NYUHSL Faculty Bibliography

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156

Molecular neurodegeneration. 2016:11(1).DOI: 10.1186/s13024-016-0126-z

Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy

Congdon, Erin E; Lin, Yan; Rajamohamedsait, Hameetha B; Shamir, Dov B; Krishnaswamy, Senthilkumar; Rajamohamedsait, Wajitha J; Rasool, Suhail; Gonzalez, Veronica; Levenga, Josien; Gu, Jiaping; Hoeffer, Charles; Sigurdsson, Einar M

BACKGROUND: A few tau immunotherapies are now in clinical trials with several more likely to be initiated in the near future. A priori, it can be anticipated that an antibody which broadly recognizes various pathological tau aggregates with high affinity would have the ideal therapeutic properties. Tau antibodies 4E6 and 6B2, raised against the same epitope region but of varying specificity and affinity, were tested for acutely improving cognition and reducing tau pathology in transgenic tauopathy mice and neuronal cultures. RESULTS: Surprisingly, we here show that one antibody, 4E6, which has low affinity for most forms of tau acutely improved cognition and reduced soluble phospho-tau, whereas another antibody, 6B2, which has high affinity for various tau species was ineffective. Concurrently, we confirmed and clarified these efficacy differences in an ex vivo model of tauopathy. Alzheimer's paired helical filaments (PHF) were toxic to the neurons and increased tau levels in remaining neurons. Both toxicity and tau seeding were prevented by 4E6 but not by 6B2. Furthermore, 4E6 reduced PHF spreading between neurons. Interestingly, 4E6's efficacy relates to its high affinity binding to solubilized PHF, whereas the ineffective 6B2 binds mainly to aggregated PHF. Blocking 4E6's uptake into neurons prevented its protective effects if the antibody was administered after PHF had been internalized. When 4E6 and PHF were administered at the same time, the antibody was protective extracellularly. CONCLUSIONS: Overall, these findings indicate that high antibody affinity for solubilized PHF predicts efficacy, and that acute antibody-mediated improvement in cognition relates to clearance of soluble phospho-tau. Importantly, both intra- and extracellular clearance pathways are in play. Together, these results have major implications for understanding the pathogenesis of tauopathies and for development of immunotherapies.

PMCID:5006503

PMID: 27578006

ISSN: 1750-1326

CID: 2232012

Scientific reports. 2016:6.DOI: 10.1038/srep19393

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

Fa, M; Puzzo, D; Piacentini, R; Staniszewski, A; Zhang, H; Baltrons, M A; Li Puma, D D; Chatterjee, I; Li, J; Saeed, F; Berman, H L; Ripoli, C; Gulisano, W; Gonzalez, J; Tian, H; Costa, J A; Lopez, P; Davidowitz, E; Yu, W H; Haroutunian, V; Brown, L M; Palmeri, A; Sigurdsson, E M; Duff, K E; Teich, A F; Honig, L S; Sierks, M; Moe, J G; D'Adamio, L; Grassi, C; Kanaan, N M; Fraser, P E; Arancio, O

Non-fibrillar soluble oligomeric forms of amyloid-beta peptide (oAbeta) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAbeta initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Abeta, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAbeta levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAbeta to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Abeta on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Abeta and tau pathology.

PMCID:4726138

PMID: 26786552

ISSN: 2045-2322

CID: 1921462

Autophagy. 2016:12(2).DOI: 10.1080/15548627.2016.1147886

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

Klionsky, Daniel J.; Abdelmohsen, Kotb; Abe, Akihisa; Abedin, Md Joynal; Abeliovich, Hagai; Arozena, Abraham Acevedo; Adachi, Hiroaki; Adams, Christopher M.; Adams, Peter D.; Adeli, Khosrow; Adhihetty, Peter J.; Adler, Sharon G.; Agam, Galila; Agarwal, Rajesh; Aghi, Manish K.; Agnello, Maria; Agostinis, Patrizia; Aguilar, Patricia V.; Aguirre-Ghiso, Julio; Airoldi, Edoardo M.; Ait-Si-Ali, Slimane; Akematsu, Takahiko; Akporiaye, Emmanuel T.; Al-Rubeai, Mohamed; Albaiceta, Guillermo M.; Albanese, Chris; Albani, Diego; Albert, Matthew L.; Aldudo, Jesus; AlgÃ¼l, Hana; Alirezaei, Mehrdad; Alloza, Iraide; Almasan, Alexandru; Almonte-Beceril, Maylin; Alnemri, Emad S.; Alonso, Covadonga; Altan-Bonnet, Nihal; Altieri, Dario C.; Alvarez, Silvia; Alvarez-Erviti, Lydia; Alves, Sandro; Amadoro, Giuseppina; Amano, Atsuo; Amantini, Consuelo; Ambrosio, Santiago; Amelio, Ivano; Amer, Amal O.; Amessou, Mohamed; Amon, Angelika; An, Zhenyi; Anania, Frank A.; Andersen, Stig U.; Andley, Usha P.; Andreadi, Catherine K.; Andrieu-Abadie, Nathalie; Anel, Alberto; Ann, David K.; Anoopkumar-Dukie, Shailendra; Antonioli, Manuela; Aoki, Hiroshi; Apostolova, Nadezda; Aquila, Saveria; Aquilano, Katia; Araki, Koichi; Arama, Eli; Aranda, Agustin; Araya, Jun; Arcaro, Alexandre; Arias, Esperanza; Arimoto, Hirokazu; Ariosa, Aileen R.; Armstrong, Jane L.; Arnould, Thierry; Arsov, Ivica; Asanuma, Katsuhiko; Askanas, Valerie; Asselin, Eric; Atarashi, Ryuichiro; Atherton, Sally S.; Atkin, Julie D.; Attardi, Laura D.; Auberger, Patrick; Auburger, Georg; Aurelian, Laure; Autelli, Riccardo; Avagliano, Laura; Avantaggiati, Maria Laura; Avrahami, Limor; Azad, Neelam; Awale, Suresh; Bachetti, Tiziana; Backer, Jonathan M.; Bae, Dong Hun; Bae, Jae Sung; Bae, Ok Nam; Bae, Soo Han; Baehrecke, Eric H.; Baek, Seung Hoon; Baghdiguian, Stephen; Bagniewska-Zadworna, Agnieszka; Bai, Hua; Bai, Jie; Bai, Xue Yuan; Bailly, Yannick; Balaji, Kithiganahalli Narayanaswamy; Balduini, Walter; Ballabio, Andrea; Balzan, Rena; Banerjee, Rajkumar; BÃ¡nhegyi, GÃ¡bor; Bao, Haijun; Barbeau, Benoit; Barrachina, Maria D.; Barreiro, Esther; Bartel, Bonnie; BartolomÃ©, Alberto; Bassham, Diane C.; Bassi, Maria Teresa; Bast, Robert C.; Basu, Alakananda; Batista, Maria Teresa; Batoko, Henri; Battino, Maurizio; Bauckman, Kyle; Baumgarner, Bradley L.; Bayer, K. Ulrich; Beale, Rupert; Beaulieu, Jean FranÃ§ois; Beck, George R.; Becker, Christoph; Beckham, J. David; BÃ©dard, Pierre AndrÃ©; Bednarski, Patrick J.; Begley, Thomas J.; Behl, Christian; Behrends, Christian; Behrens, Georg M.N.; Behrns, Kevin E.; Bejarano, Eloy; Belaid, Amine; Belleudi, Francesca; BÃ©nard, Giovanni; Berchem, Guy; Bergamaschi, Daniele; Bergami, Matteo; Berkhout, Ben; Berliocchi, Laura; Bernard, AmÃ©lie; Bernard, Monique; Bernassola, Francesca; Bertolotti, Anne; Bess, Amanda S.; Besteiro, SÃ©bastien; Bettuzzi, Saverio; Bhalla, Savita; Bhattacharyya, Shalmoli; Bhutia, Sujit K.; Biagosch, Caroline; Bianchi, Michele Wolfe; Biard-Piechaczyk, Martine; Billes, Viktor; Bincoletto, Claudia; Bingol, Baris; Bird, Sara W.; Bitoun, Marc; Bjedov, Ivana; Blackstone, Craig; Blanc, Lionel; Blanco, Guillermo A.; Blomhoff, Heidi Kiil; Boada-Romero, Emilio; Bockler, Stefan; Boes, Marianne; Boesze-Battaglia, Kathleen; Boise, Lawrence H.; Bolino, Alessandra; Boman, Andrea; Bonaldo, Paolo; Bordi, Matteo; Bosch, JÃ¼rgen; Botana, Luis M.; Botti, Joelle; Bou, German; BouchÃ©, Marina; Bouchecareilh, Marion; Boucher, Marie JosÃ©e; Boulton, Michael E.; Bouret, Sebastien G.; Boya, Patricia; Boyer-Guittaut, MichaÃ«l; Bozhkov, Peter V.; Brady, Nathan; Braga, Vania M.M.; Brancolini, Claudio; Braus, Gerhard H.; Bravosan-Pedro, JosÃ© M.; Brennan, Lisa A.; Bresnick, Emery H.; Brest, Patrick; Bridges, Dave; Bringer, Marie AgnÃ¨s; Brini, Marisa; Brito, Glauber C.; Brodin, Bertha; Brookes, Paul S.; Brown, Eric J.; Brown, Karen; Broxmeyer, Hal E.; Bruhat, Alain; Brum, Patricia Chakur; Brumell, John H.; Brunetti-Pierri, Nicola; Bryson-Richardson, Robert J.; Buch, Shilpa; Buchan, Alastair M.; Budak, Hikmet; Bulavin, Dmitry V.; Bultman, Scott J.; Bultynck, Geert; Bumbasirevic, Vladimir; Burelle, Yan; Burke, Robert E.; Burmeister, Margit; BÃ¼tikofer, Peter; Caberlotto, Laura; Cadwell, Ken; Cahova, Monika; Cai, Dongsheng; Cai, Jingjing; Cai, Qian; Calatayud, Sara; Camougrand, Nadine; Campanella, Michelangelo; Campbell, Grant R.; Campbell, Matthew; Campello, Silvia; Candau, Robin; Caniggia, Isabella; Cantoni, Lavinia; Cao, Lizhi; Caplan, Allan B.; Caraglia, Michele; Cardinali, Claudio; Cardoso, Sandra Morais; Carew, Jennifer S.; Carleton, Laura A.; Carlin, Cathleen R.; Carloni, Silvia; Carlsson, Sven R.; Carmona-Gutierrez, Didac; Carneiro, Leticia A.M.; Carnevali, Oliana; Carra, Serena; Carrier, Alice; Carroll, Bernadette; Casas, Caty; Casas, Josefina; Cassinelli, Giuliana; Castets, Perrine; Castro-Obregon, Susana; Cavallini, Gabriella; Ceccherini, Isabella; Cecconi, Francesco; Cederbaum, Arthur I.; CeÃ±a, Valentin; Cenci, Simone; Cerella, Claudia; Cervia, Davide; Cetrullo, Silvia; Chaachouay, Hassan; Chae, Han Jung; Chagin, Andrei S.; Chai, Chee Yin; Chakrabarti, Gopal; Chamilos, Georgios; Chan, Edmond Y.W.; Chan, Matthew T.V.; Chandra, Dhyan; Chandra, Pallavi; Chang, Chih Peng; Chang, Raymond Chuen Chung; Chang, Ta Yuan; Chatham, John C.; Chatterjee, Saurabh; Chauhan, Santosh; Che, Yongsheng; Cheetham, Michael E.; Cheluvappa, Rajkumar; Chen, Chun Jung; Chen, Gang; Chen, Guang Chao; Chen, Guoqiang; Chen, Hongzhuan; Chen, Jeff W.; Chen, Jian Kang; Chen, Min; Chen, Mingzhou; Chen, Peiwen; Chen, Qi; Chen, Quan; Chen, Shang Der; Chen, Si; Chen, Steve S.L.; Chen, Wei; Chen, Wei Jung; Chen, Wen Qiang; Chen, Wenli; Chen, Xiangmei; Chen, Yau Hung; Chen, Ye Guang; Chen, Yin; Chen, Yingyu; Chen, Yongshun; Chen, Yu Jen; Chen, Yue Qin; Chen, Yujie; Chen, Zhen; Chen, Zhong; Cheng, Alan; Cheng, Christopher H.K.; Cheng, Hua; Cheong, Heesun; Cherry, Sara; Chesney, Jason; Cheung, Chun Hei Antonio; Chevet, Eric; Chi, Hsiang Cheng; Chi, Sung Gil; Chiacchiera, Fulvio; Chiang, Hui Ling; Chiarelli, Roberto; Chiariello, Mario; Chieppa, Marcello; Chin, Lih Shen; Chiong, Mario; Chiu, Gigi N.C.; Cho, Dong Hyung; Cho, Ssang Goo; Cho, William C.; Cho, Yong Yeon; Cho, Young Seok; Choi, Augustine M.K.; Choi, Eui Ju; Choi, Eun Kyoung; Choi, Jayoung; Choi, Mary E.; Choi, Seung Il; Chou, Tsui Fen; Chouaib, Salem; Choubey, Divaker; Choubey, Vinay; Chow, Kuan Chih; Chowdhury, Kamal; Chu, Charleen T.; Chuang, Tsung Hsien; Chun, Taehoon; Chung, Hyewon; Chung, Taijoon; Chung, Yuen Li; Chwae, Yong Joon; Cianfanelli, Valentina; Ciarcia, Roberto; Ciechomska, Iwona A.; Ciriolo, Maria Rosa; Cirone, Mara; Claerhout, Sofie; Clague, Michael J.; Clï¿½ ria, Joan; Clarke, Peter G.H.; Clarke, Robert; Clementi, Emilio; Cleyrat, CÃ©dric; Cnop, Miriam; Coccia, Eliana M.; Cocco, Tiziana; Codogno, Patrice; Coers, Jorn; Cohen, Ezra E.W.; Colecchia, David; Coletto, Luisa; Coll, Nuria S.; Colucci-Guyon, Emma; Comincini, Sergio; Condello, Maria; Cook, Katherine L.; Coombs, Graham H.; Cooper, Cynthia D.; Cooper, J. Mark; Coppens, Isabelle; Corasaniti, Maria Tiziana; Corazzari, Marco; Corbalan, Ramon; Corcelle-Termeau, Elisabeth; Cordero, Mario D.; Corral-Ramos, Cristina; Corti, Olga; Cossarizza, Andrea; Costelli, Paola; Costes, Safia; Cotman, Susan L.; Coto-Montes, Ana; Cottet, Sandra; Couve, Eduardo; Covey, Lori R.; Cowart, L. Ashley; Cox, Jeffery S.; Coxon, Fraser P.; Coyne, Carolyn B.; Cragg, Mark S.; Craven, Rolf J.; Crepaldi, Tiziana; Crespo, Jose L.; Criollo, Alfredo; Crippa, Valeria; Cruz, Maria Teresa; Cuervo, Ana Maria; Cuezva, Jose M.; Cui, Taixing; Cutillas, Pedro R.; Czaja, Mark J.; Czyzyk-Krzeska, Maria F.; Dagda, Ruben K.; Dahmen, Uta; Dai, Chunsun; Dai, Wenjie; Dai, Yun; Dalby, Kevin N.; Valle, Luisa Dalla; Dalmasso, Guillaume; D'amelio, Marcello; Damme, Markus; Darfeuille-Michaud, Arlette; Dargemont, Catherine; Darley-Usmar, Victor M.; Dasarathy, Srinivasan; Dasgupta, Biplab; Dash, Srikanta; Dass, Crispin R.; Davey, Hazel Marie; Davids, Lester M.; DÃ¡vila, David; Davis, Roger J.; Dawson, Ted M.; Dawson, Valina L.; Daza, Paula; de Belleroche, Jackie; de Figueiredo, Paul; de Figueiredo, Regina Celia Bressan Queiroz; de la Fuente, JosÃ©; De Martino, Luisa; De Matteis, Antonella; De Meyer, Guido R.Y.; De Milito, Angelo; De Santi, Mauro; de Souza, Wanderley; De Tata, Vincenzo; De Zio, Daniela; Debnath, Jayanta; Dechant, Reinhard; Decuypere, Jean Paul; Deegan, Shane; Dehay, Benjamin; Del Bello, Barbara; Del Re, Dominic P.; Delage-Mourroux, RÃ©gis; Delbridge, Lea M.D.; Deldicque, Louise; Delorme-Axford, Elizabeth; Deng, Yizhen; Dengjel, Joern; Denizot, Melanie; Dent, Paul; Der, Channing J.; Deretic, Vojo; Derrien, BenoÃ®t; Deutsch, Eric; Devarenne, Timothy P.; Devenish, Rodney J.; Di Bartolomeo, Sabrina; Di Daniele, Nicola; Di Domenico, Fabio; Di Nardo, Alessia; Di Paola, Simone; Di Pietro, Antonio; Di Renzo, Livia; Di Antonio, Aaron; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T.; Diaz-Nido, Javier; Dickey, Chad A.; Dickson, Robert C.; Diederich, Marc; Digard, Paul; Dikic, Ivan; Dinesh-Kumar, Savithrama P.; Ding, Chan; Ding, Wen Xing; Ding, Zufeng; Dini, Luciana; Distler, Jorg H.W.; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dmytruk, Kostyantyn; Dobson, Renwick C.J.; Doetsch, Volker; Dokladny, Karol; Dokudovskaya, Svetlana; Donadelli, Massimo; Dong, X. Charlie; Dong, Xiaonan; Dong, Zheng; Donohue, Terrence M.; Donohue-Jr, Terrence M.; Doran, Kelly S.; D'orazi, Gabriella; Dorn, Gerald W.; Dosenko, Victor; Dridi, Sami; Drucker, Liat; Du, Jie; Du, Li Lin; Du, Lihuan; du Toit, AndrÃ©; Dua, Priyamvada; Duan, Lei; Duann, Pu; Dubey, Vikash Kumar; Duchen, Michael R.; Duchosal, Michel A.; Duez, Helene; Dugail, Isabelle; Dumit, VerÃ³nica I.; Duncan, Mara C.; Dunlop, Elaine A.; Dunn, William A.; Dupont, Nicolas; Dupuis, Luc; DurÃ¡n, Raul V.; Durcan, Thomas M.; Duvezin-Caubet, StÃ©phane; Duvvuri, Umamaheswar; Eapen, Vinay; Ebrahimi-Fakhari, Darius; Echard, Arnaud; Eckhart, Leopold; Edelstein, Charles L.; Edinger, Aimee L.; Eichinger, Ludwig; Eisenberg, Tobias; Eisenberg-Lerner, Avital; Eissa, N. Tony; El-Deiry, Wafik S.; El-Khoury, Victoria; Elazar, Zvulun; Eldar-Finkelman, Hagit; Elliott, Chris J.H.; Emanuele, Enzo; Emmenegger, Urban; Engedal, Nikolai; Engelbrecht, Anna Mart; Engelender, Simone; Enserink, Jorrit M.; Erdmann, Ralf; Erenpreisa, Jekaterina; Eri, Rajaraman; Eriksen, Jason L.; Erman, Andreja; Escalante, Ricardo; Eskelinen, Eeva Liisa; Espert, Lucile; Esteban-Martinez, Lorena; Evans, Thomas J.; Fabri, Mario; Fabrias, Gemma; Fabrizi, Cinzia; Facchiano, Antonio; FÃ¦rgeman, Nils J.; Faggioni, Alberto; Fairlie, W. Douglas; Fan, Chunhai; Fan, Daping; Fan, Jie; Fang, Shengyun; Fanto, Manolis; Fanzani, Alessandro; Farkas, Thomas; Faure, Mathias; Favier, Francois B.; Fearnhead, Howard; Federici, Massimo; Fei, Erkang; Felizardo, Tania C.; Feng, Hua; Feng, Yibin; Feng, Yuchen; Ferguson, Thomas A.; FernÃ¡ndez, Ãlvaro F.; Fernandez-Barrena, Maite G.; Fernandez-Checa, Jose C.; FernÃ¡ndez-LÃ³pez, Arsenio; Fernandez-Zapico, Martin E.; Feron, Olivier; Ferraro, Elisabetta; Ferreira-Halder, Carmen Verissima; Fesus, Laszlo; Feuer, Ralph; Fiesel, Fabienne C.; Filippi-Chiela, Eduardo C.; Filomeni, Giuseppe; Fimia, Gian Maria; Fingert, John H.; Finkbeiner, Steven; Finkel, Toren; Fiorito, Filomena; Fisher, Paul B.; Flajolet, Marc; Flamigni, Flavio; Florey, Oliver; Florio, Salvatore; Floto, R. Andres; Folini, Marco; Follo, Carlo; Fon, Edward A.; Fornai, Francesco; Fortunato, Franco; Fraldi, Alessandro; Franco, Rodrigo; Francois, Arnaud; FranÃ§ois, AurÃ©lie; Frankel, Lisa B.; Fraser, Iain D.C.; Frey, Norbert; Freyssenet, Damien G.; Frezza, Christian; Friedman, Scott L.; Frigo, Daniel E.; Fu, Dongxu; Fuentes, JosÃ© M.; Fueyo, Juan; Fujitani, Yoshio; Fujiwara, Yuuki; Fujiya, Mikihiro; Fukuda, Mitsunori; Fulda, Simone; Fusco, Carmela; Gabryel, Bozena; Gaestel, Matthias; Gailly, Philippe; Gajewska, Malgorzata; Galadari, Sehamuddin; Galili, Gad; Galindo, Inmaculada; Galindo, Maria F.; Galliciotti, Giovanna; Galluzzi, Lorenzo; Galluzzi, Luca; Galy, Vincent; Gammoh, Noor; Gandy, Sam; Ganesan, Anand K.; Ganesan, Swamynathan; Ganley, Ian G.; GannagÃ©, Monique; Gao, Fen Biao; Gao, Feng; Gao, Jian Xin; Nannig, Lorena Garcia; VÃ©scovi, Eleonora Garcia; Garcia-Macia, Marina; Garcia-Ruiz, Carmen; Garg, Abhishek D.; Garg, Pramod Kumar; Gargini, Ricardo; Gassen, Nils Christian; Gatica, DamiÃ¡n; Gatti, Evelina; Gavard, Julie; Gavathiotis, Evripidis; Ge, Liang; Ge, Pengfei; Ge, Shengfang; Gean, Po Wu; Gelmetti, Vania; Genazzani, Armando A.; Geng, Jiefei; Genschik, Pascal; Gerner, Lisa; Gestwicki, Jason E.; Gewirtz, David A.; Ghavami, Saeid; Ghigo, Eric; Ghosh, Debabrata; Giammarioli, Anna Maria; Giampieri, Francesca; Giampietri, Claudia; Giatromanolaki, Alexandra; Gibbings, Derrick J.; Gibellini, Lara; Gibson, Spencer B.; Ginet, Vanessa; Giordano, Antonio; Giorgini, Flaviano; Giovannetti, Elisa; Girardin, Stephen E.; Gispert, Suzana; Giuliano, Sandy; Gladson, Candece L.; Glavic, Alvaro; Gleave, Martin; Godefroy, Nelly; Gogal, Robert M.; Gokulan, Kuppan; Goldman, Gustavo H.; Goletti, Delia; Goligorsky, Michael S.; Gomes, Aldrin V.; Gomes, Ligia C.; Gomez, Hernando; Gomez-Manzano, Candelaria; GÃ³mez-SÃ¡nchez, RubÃ©n; GonÃ§alves, Dawit A.P.; Goncu, Ebru; Gong, Qingqiu; Gongora, CÃ©line; Gonzalez, Carlos B.; Gonzalez-Alegre, Pedro; Gonzalez-Cabo, Pilar; GonzÃ¡lez-Polo, Rosa Ana; Goping, Ing Swie; Gorbea, Carlos; Gorbunov, Nikolai V.; Goring, Daphne R.; Gorman, Adrienne M.; Gorski, Sharon M.; Goruppi, Sandro; Goto-Yamada, Shino; Gotor, Cecilia; Gottlieb, Roberta A.; Gozes, Illana; Gozuacik, Devrim; Graba, Yacine; Graef, Martin; Granato, Giovanna E.; Grant, Gary Dean; Grant, Steven; Gravina, Giovanni Luca; Green, Douglas R.; Greenhough, Alexander; Greenwood, Michael T.; Grimaldi, Benedetto; Gros, FrÃ©dÃ©ric; Grose, Charles; Groulx, Jean Francois; Gruber, Florian; Grumati, Paolo; Grune, Tilman; Guan, Jun Lin; Guan, Kun Liang; Guerra, Barbara; Guillen, Carlos; Gulshan, Kailash; Gunst, Jan; Guo, Chuanyong; Guo, Lei; Guo, Ming; Guo, Wenjie; Guo, Xu Guang; Gust, Andrea A.; Gustafsson, Ã…sa B.; Gutierrez, Elaine; Gutierrez, Maximiliano G.; Gwak, Ho Shin; Haas, Albert; Haber, James E.; Hadano, Shinji; Hagedorn, Monica; Hahn, David R.; Halayko, Andrew J.; Hamacher-Brady, Anne; Hamada, Kozo; Hamai, Ahmed; Hamann, Andrea; Hamasaki, Maho; Hamer, Isabelle; Hamid, Qutayba; Hammond, Ester M.; Han, Feng; Han, Weidong; Handa, James T.; Hanover, John A.; Hansen, Malene; Harada, Masaru; Harhaji-Trajkovic, Ljubica; Harper, J. Wade; Harrath, Abdel Halim; Harris, Adrian L.; Harris, James; Hasler, Udo; Hasselblatt, Peter; Hasui, Kazuhisa; Hawley, Robert G.; Hawley, Teresa S.; He, Congcong; He, Cynthia Y.; He, Fengtian; He, Gu; He, Rong Rong; He, Xian Hui; He, You Wen; He, Yu Ying; Heath, Joan K.; HÃ©bert, Marie JosÃ©e; Heinzen, Robert A.; Helgason, Gudmundur Vignir; Hensel, Michael; Henske, Elizabeth P.; Her, Chengtao; Herman, Paul K.; HernÃ¡ndez, Agustin; Hernandez, Carlos; HernÃ¡ndez-Tiedra, Sonia; Hetz, Claudio; Hiesinger, P. Robin; Higaki, Katsumi; Hilfiker, Sabine; Hill, Bradford G.; Hill, Joseph A.; Hill, William D.; Hino, Keisuke; Hofius, Daniel; Hofman, Paul; Hoglinger, GÃ¼nter U.; Hohfeld, Jorg; Holz, Marina K.; Hong, Yonggeun; Hood, David A.; Hoozemans, Jeroen J.M.; Hoppe, Thorsten; Hsu, Chin; Hsu, Chin Yuan; Hsu, Li Chung; Hu, Dong; Hu, Guochang; Hu, Hong Ming; Hu, Hongbo; Hu, Ming Chang; Hu, Yu Chen; Hu, Zhuo Wei; Hua, Fang; Hua, Ya; Huang, Canhua; Huang, Huey Lan; Huang, Kuo How; Huang, Kuo Yang; Huang, Shile; Huang, Shiqian; Huang, Wei Pang; Huang, Yi Ran; Huang, Yong; Huang, Yunfei; Huber, Tobias B.; Huebbe, Patricia; Huh, Won Ki; Hulmi, Juha J.; Hur, Gang Min; Hurley, James H.; Husak, Zvenyslava; Hussain, Sabah N.A.; Hussain, Salik; Hwang, Jung Jin; Hwang, Seungmin; Hwang, Thomas I.S.; Ichihara, Atsuhiro; Imai, Yuzuru; Imbriano, Carol; Inomata, Megumi; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L.; Iozzo, Renato V.; Ip, Nancy Y.; Irazoqui, Javier E.; Iribarren, Pablo; Isaka, Yoshitaka; Isakovic, Aleksandra J.; Ischiropoulos, Harry; Isenberg, Jeffrey S.; Ishaq, Mohammad; Ishida, Hiroyuki; Ishii, Isao; Ishmael, Jane E.; Isidoro, Ciro; Isobe, Ken Ichi; Isono, Erika; Issazadeh-Navikas, Shohreh; Itahana, Koji; Itakura, Eisuke; Ivanov, Andrei I.; Iyer, Anand Krishnan V.; Izquierdo, JosÃ© M.; Izumi, Yotaro; Izzo, Valentina; JÃ¤Ã¤ttelÃ¤, Marja; Jaber, Nadia; Jackson, Daniel John; Jackson, William T.; Jacob, Tony George; Jacques, Thomas S.; Jagannath, Chinnaswamy; Jain, Ashish; Jana, Nihar Ranjan; Jang, Byoung Kuk; Jani, Alkesh; Janji, Bassam; Jannig, Paulo Roberto; Jansson, Patric J.; Jean, Steve; Jendrach, Marina; Jeon, Ju Hong; Jessen, Niels; Jeung, Eui Bae; Jia, Kailiang; Jia, Lijun; Jiang, Hong; Jiang, Hongchi; Jiang, Liwen; Jiang, Teng; Jiang, Xiaoyan; Jiang, Xuejun; Jiang, Ying; Jiang, Yongjun; JimÃ©nez, Alberto; Jin, Cheng; Jin, Hongchuan; Jin, Lei; Jin, Meiyan; Jin, Shengkan; Jinwal, Umesh Kumar; Jo, Eun Kyeong; Johansen, Terje; Johnson, Daniel E.; Johnson, Gail V.W.; Johnson, James D.; Jonasch, Eric; Jones, Chris; Joosten, Leo A.B.; Jordan, Joaquin; Joseph, Anna Maria; Joseph, Bertrand; Joubert, Annie M.; Ju, Dianwen; Ju, Jingfang; Juan, Hsueh Fen; Juenemann, Katrin; JuhÃ¡sz, GÃ¡bor; Jung, Hye Seung; Jung, Jae U.; Jung, Yong Keun; Jungbluth, Heinz; Justice, Matthew J.; Jutten, Barry; Kaakoush, Nadeem O.; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kaeffer, Bertrand; KÃ¥gedal, Katarina; Kahana, Alon; Kajimura, Shingo; Kakhlon, Or; Kalia, Manjula; Kalvakolanu, Dhan V.; Kamada, Yoshiaki; Kambas, Konstantinos; Kaminskyy, Vitaliy O.; Kampinga, Harm H.; Kandouz, Mustapha; Kang, Chanhee; Kang, Rui; Kang, Tae Cheon; Kanki, Tomotake; Kanneganti, Thirumala Devi; Kanno, Haruo; Kanthasamy, Anumantha G.; Kantorow, Marc; Kaparakis-Liaskos, Maria; Kapuy, Orsolya; Karantza, Vassiliki; Karim, Md Razaul; Karmakar, Parimal; Kaser, Arthur; Kaushik, Susmita; Kawula, Thomas; Kaynar, A. Murat; Ke, Po Yuan; Ke, Zun Ji; Kehrl, John H.; Keller, Kate E.; Kemper, Jongsook Kim; Kenworthy, Anne K.; Kepp, Oliver; Kern, Andreas; Kesari, Santosh; Kessel, David; Ketteler, Robin; Kettelhut, Isis do Carmo; Khambu, Bilon; Khan, Muzamil Majid; Khandelwal, Vinoth K.M.; Khare, Sangeeta; Kiang, Juliann G.; Kiger, Amy A.; Kihara, Akio; Kim, Arianna L.; Kim, Cheol Hyeon; Kim, Deok Ryong; Kim, Do Hyung; Kim, Eung Kweon; Kim, Hye Young; Kim, Hyung Ryong; Kim, Jae Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, Jin Hyoung; Kim, Kwang Woon; Kim, Michael D.; Kim, Moon Moo; Kim, Peter K.; Kim, Seong Who; Kim, Soo Youl; Kim, Yong Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C.; Kimura, Tomonori; King, Jason S.; Kirkegaard, Karla; Kirkin, Vladimir; Kirshenbaum, Lorrie A.; Kishi, Shuji; Kitajima, Yasuo; Kitamoto, Katsuhiko; Kitaoka, Yasushi; Kitazato, Kaio; Kley, Rudolf A.; Klimecki, Walter T.; Klinkenberg, Michael; Klucken, Jochen; KnÃ¦velsrud, Helene; Knecht, Erwin; Knuppertz, Laura; Ko, Jiunn Liang; Kobayashi, Satoru; Koch, Jan C.; Koechlin-Ramonatxo, Christelle; Koenig, Ulrich; Koh, Young Ho; Kohler, Katja; Kohlwein, Sepp D.; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Dexin; Kong, Hee Jeong; Konstantakou, Eumorphia G.; Kopp, Benjamin T.; Korcsmaros, Tamas; Korhonen, Laura; Korolchuk, Viktor I.; Koshkina, Nadya V.; Kou, Yanjun; Koukourakis, Michael I.; Koumenis, Constantinos; KovÃ¡cs, Attila L.; KovÃ¡cs, Tibor; Kovacs, Werner J.; Koya, Daisuke; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kravic-Stevovic, Tamara; Krek, Wilhelm; Kretz-Remy, Carole; Krick, Roswitha; Krishnamurthy, Malathi; Kriston-Vizi, Janos; Kroemer, Guido; Kruer, Michael C.; Kruger, Rejko; Ktistakis, Nicholas T.; Kuchitsu, Kazuyuki; Kuhn, Christian; Kumar, Addanki Pratap; Kumar, Anuj; Kumar, Ashok; Kumar, Deepak; Kumar, Dhiraj; Kumar, Rakesh; Kumar, Sharad; Kundu, Mondira; Kung, Hsing Jien; Kuno, Atsushi; Kuo, Sheng Han; Kuret, Jeff; Kurz, Tino; Kwok, Terry; Kwon, Taeg Kyu; Kwon, Yong Tae; Kyrmizi, Irene; La Spada, Albert R.; Lafont, Frank; Lahm, Tim; Lakkaraju, Aparna; Lam, Truong; Lamark, Trond; Lancel, Steve; Landowski, Terry H.; Lane, Darius J.R.; Lane, Jon D.; Lanzi, Cinzia; Lapaquette, Pierre; Lapierre, Louis R.; Laporte, Jocelyn; Laukkarinen, Johanna; Laurie, Gordon W.; Lavandero, Sergio; Lavie, Lena; Lavoie, Matthew J.; Law, Betty Yuen Kwan; Law, Helen Ka Wai; Law, Kelsey B.; Layfield, Robert; Lazo, Pedro A.; Le Cam, Laurent; Le Roch, Karine G.; Le Stunff, HervÃ©; Leardkamolkarn, Vijittra; Lecuit, Marc; Lee, Byung Hoon; Lee, Che Hsin; Lee, Erinna F.; Lee, Gyun Min; Lee, He Jin; Lee, Hsinyu; Lee, Jae Keun; Lee, Jongdae; Lee, Ju Hyun; Lee, Jun Hee; Lee, Michael; Lee, Myung Shik; Lee, Patty J.; Lee, Sam W.; Lee, Seung Jae; Lee, Shiow Ju; Lee, Stella Y.; Lee, Sug Hyung; Lee, Sung Sik; Lee, Sung Joon; Lee, Sunhee; Lee, Ying Ray; Lee, Yong J.; Lee, Young H.; Leeuwenburgh, Christiaan; Lefort, Sylvain; Legouis, Renaud; Lei, Jinzhi; Lei, Qun Ying; Leib, David A.; Leibowitz, Gil; Lekli, Istvan; Lemaire, StÃ©phane D.; Lemasters, John J.; Lemberg, Marius K.; Lemoine, Antoinette; Leng, Shuilong; Lenz, Guido; Lenzi, Paola; Lerman, Lilach O.; Barbato, Daniele Lettieri; Leu, Julia I.Ju; Leung, Hing Y.; Levine, Beth; Lewis, Patrick A.; Lezoualch, Frank; Li, Chi; Li, Faqiang; Li, Feng Jun; Li, Jun; Li, Ke; Li, Lian; Li, Min; Li, Qiang; Li, Rui; Li, Sheng; Li, Wei; Li, Xiaotao; Li, Yumin; Lian, Jiqin; Liang, Chengyu; Liang, Qiangrong; Liao, Yulin; Liberal, Joana; Liberski, Pawel P.; Lie, Pearl; Lieberman, Andrew P.; Lim, Hyunjung Jade; Lim, Kah Leong; Lim, Kyu; Lima, Raquel T.; Lin, Chang Shen; Lin, Chiou Feng; Lin, Fang; Lin, Fangming; Lin, Fu Cheng; Lin, Kui; Lin, Kwang Huei; Lin, Pei Hui; Lin, Tianwei; Lin, Wan Wan; Lin, Yee Shin; Lin, Yong; Linden, Rafael; Lindholm, Dan; Lindqvist, Lisa M.; Lingor, Paul; Linkermann, Andreas; Liotta, Lance A.; Lipinski, Marta M.; Lira, Vitor A.; Lisanti, Michael P.; Liton, Paloma B.; Liu, Bo; Liu, Chong; Liu, Chun Feng; Liu, Fei; Liu, Hung Jen; Liu, Jianxun; Liu, Jing Jing; Liu, Jing Lan; Liu, Ke; Liu, Leyuan; Liu, Liang; Liu, Quentin; Liu, Rong Yu; Liu, Shiming; Liu, Shuwen; Liu, Wei; Liu, Xian De; Liu, Xiangguo; Liu, Xiao Hong; Liu, Xinfeng; Liu, Xu; Liu, Xueqin; Liu, Yang; Liu, Yule; Liu, Zexian; Liu, Zhe; Liuzzi, Juan P.; Lizard, GÃ©rard; Ljujic, Mila; Lodhi, Irfan J.; Logue, Susan E.; Lokeshwar, Bal L.; Long, Yun Chau; Lonial, Sagar; Loos, Benjamin; LÃ³pez-Otin, Carlos; LÃ³pez-Vicario, Cristina; Lorente, Mar; Lorenzi, Philip L.; LÃµrincz, PÃ©ter; Los, Marek; Lotze, Michael T.; Lovat, Penny E.; Lu, Binfeng; Lu, Bo; Lu, Jiahong; Lu, Qing; Lu, She Min; Lu, Shuyan; Lu, Yingying; Luciano, FrÃ©dÃ©ric; Luckhart, Shirley; Lucocq, John Milton; Ludovico, Paula; Lugea, Aurelia; Lukacs, Nicholas W.; Lum, Julian J.; Lund, Anders H.; Luo, Honglin; Luo, Jia; Luo, Shouqing; Luparello, Claudio; Lyons, Timothy; Ma, Jianjie; Ma, Yi; Ma, Yong; Ma, Zhenyi; Machado, Juliano; Machado-Santelli, Glaucia M.; Macian, Fernando; MacIntosh, Gustavo C.; MacKeigan, Jeffrey P.; Macleod, Kay F.; MacMicking, John D.; MacMillan-Crow, Lee Ann; Madeo, Frank; Madesh, Muniswamy; Madrigal-Matute, Julio; Maeda, Akiko; Maeda, Tatsuya; Maegawa, Gustavo; Maellaro, Emilia; Maes, Hannelore; MagariÃ±os, Marta; Maiese, Kenneth; Maiti, Tapas K.; Maiuri, Luigi; Maiuri, Maria Chiara; Maki, Carl G.; Malli, Roland; Malorni, Walter; Maloyan, Alina; Mami-Chouaib, Fathia; Man, Na; Mancias, Joseph D.; Mandelkow, Eva Maria; Mandell, Michael A.; Manfredi, Angelo A.; ManiÃ©, Serge N.; Manzoni, Claudia; Mao, Kai; Mao, Zixu; Mao, Zong Wan; Marambaud, Philippe; Marconi, Anna Maria; Marelja, Zvonimir; Marfe, Gabriella; Margeta, Marta; Margittai, Eva; Mari, Muriel; Mariani, Francesca V.; Marin, Concepcio; Marinelli, Sara; MariÃ±o, Guillermo; Markovic, Ivanka; Marquez, Rebecca; Martelli, Alberto M.; Martens, Sascha; Martin, Katie R.; Martin, Seamus J.; Martin, Shaun; Martin-Acebes, Miguel A.; Martin-Sanz, Paloma; Martinand-Mari, Camille; Martinet, Wim; Martinez, Jennifer; Martinez-Lopez, Nuria; Martinez-Outschoorn, Ubaldo; Martinez-VelÃ¡zquez, MoisÃ©s; Martinez-Vicente, Marta; Martins, Waleska Kerllen; Mashima, Hirosato; Mastrianni, James A.; Matarese, Giuseppe; Matarrese, Paola; Mateo, Roberto; Matoba, Satoaki; Matsumoto, Naomichi; Matsushita, Takehiko; Matsuura, Akira; Matsuzawa, Takeshi; Mattson, Mark P.; Matus, Soledad; Maugeri, Norma; Mauvezin, Caroline; Mayer, Andreas; Maysinger, Dusica; Mazzolini, Guillermo D.; McBrayer, Mary Kate; McCall, Kimberly; McCormick, Craig; McInerney, Gerald M.; McIver, Skye C.; McKenna, Sharon; McMahon, John J.; McNeish, Iain A.; Mechta-Grigoriou, Fatima; Medema, Jan Paul; Medina, Diego L.; Megyeri, Klara; Mehrpour, Maryam; Mehta, Jawahar L.; Mei, Yide; Meier, Ute Christiane; Meijer, Alfred J.; MelÃ©ndez, Alicia; Melino, Gerry; Melino, Sonia; de Melo, Edesio Jose Tenorio; Mena, Maria A.; Meneghini, Marc D.; Menendez, Javier A.; Menezes, Regina; Meng, Liesu; Meng, Ling Hua; Meng, Songshu; Menghini, Rossella; Menko, A. Sue; Menna-Barreto, Rubem F.S.; Menon, Manoj B.; Meraz-Rios, Marco A.; Merla, Giuseppe; Merlini, Luciano; Merlot, Angelica M.; Meryk, Andreas; Meschini, Stefania; Meyer, Joel N.; Mi, Man Tian; Miao, Chao Yu; Micale, Lucia; Michaeli, Simon; Michiels, Carine; Migliaccio, Anna Rita; Mihailidou, Anastasia Susie; Mijaljica, Dalibor; Mikoshiba, Katsuhiko; Milan, Enrico; Miller-Fleming, Leonor; Mills, Gordon B.; Mills, Ian G.; Minakaki, Georgia; Minassian, Berge A.; Ming, Xiu Fen; Minibayeva, Farida; Minina, Elena A.; Mintern, Justine D.; Minucci, Saverio; Miranda-Vizuete, Antonio; Mitchell, Claire H.; Miyamoto, Shigeki; Miyazawa, Keisuke; Mizushima, Noboru; Mnich, Katarzyna; Mograbi, Baharia; Mohseni, Simin; Moita, Luis Ferreira; Molinari, Marco; Molinari, Maurizio; MÃ¸ller, Andreas Buch; Mollereau, Bertrand; Mollinedo, Faustino; Mongillo, Marco; Monick, Martha M.; Montagnaro, Serena; Montell, Craig; Moore, Darren J.; Moore, Michael N.; Mora-Rodriguez, Rodrigo; Moreira, Paula I.; Morel, Etienne; Morelli, Maria Beatrice; Moreno, Sandra; Morgan, Michael J.; Moris, Arnaud; Moriyasu, Yuji; Morrison, Janna L.; Morrison, Lynda A.; Morselli, Eugenia; Moscat, Jorge; Moseley, Pope L.; Mostowy, Serge; Motori, Elisa; Mottet, Denis; Mottram, Jeremy C.; Moussa, Charbel E.H.; Mpakou, Vassiliki E.; Mukhtar, Hasan; Levy, Jean M.Mulcahy; Muller, Sylviane; MuÃ±oz-Moreno, Raquel; MuÃ±oz-Pinedo, Cristina; MÃ¼nz, Christian; Murphy, Maureen E.; Murray, James T.; Murthy, Aditya; Mysorekar, Indira U.; Nabi, Ivan R.; Nabissi, Massimo; Nader, Gustavo A.; Nagahara, Yukitoshi; Nagai, Yoshitaka; Nagata, Kazuhiro; Nagelkerke, Anika; Nagy, PÃ©ter; Naidu, Samisubbu R.; Nair, Sreejayan; Nakano, Hiroyasu; Nakatogawa, Hitoshi; Nanjundan, Meera; Napolitano, Gennaro; Naqvi, Naweed I.; Nardacci, Roberta; Narendra, Derek P.; Narita, Masashi; Nascimbeni, Anna Chiara; Natarajan, Ramesh; Navegantes, Luiz C.; Nawrocki, Steffan T.; Nazarko, Taras Y.; Nazarko, Volodymyr Y.; Neill, Thomas; Neri, Luca M.; Netea, Mihai G.; Netea-Maier, Romana T.; Neves, Bruno M.; Ney, Paul A.; Nezis, Ioannis P.; Nguyen, Hang T.T.; Nguyen, Huu Phuc; Nicot, Anne Sophie; Nilsen, Hilde; Nilsson, Per; Nishimura, Mikio; Nishino, Ichizo; Niso-Santano, Mireia; Niu, Hua; Nixon, Ralph A.; Njar, Vincent C.O.; Noda, Takeshi; Noegel, Angelika A.; Nolte, Elsie Magdalena; Norberg, Erik; Norga, Koenraad K.; Noureini, Sakineh Kazemi; Notomi, Shoji; Notterpek, Lucia; Nowikovsky, Karin; Nukina, Nobuyuki; NÃ¼rnberger, Thorsten; O'donnell, Valerie B.; O'donovan, Tracey; O'dwyer, Peter J.; Oehme, Ina; Oeste, Clara L.; Ogawa, Michinaga; Ogretmen, Besim; Ogura, Yuji; Oh, Young J.; Ohmuraya, Masaki; Ohshima, Takayuki; Ojha, Rani; Okamoto, Koji; Okazaki, Toshiro; Oliver, F. Javier; Ollinger, Karin; Olsson, Stefan; Orban, Daniel P.; Ordonez, Paulina; Orhon, Idil; Orosz, Laszlo; O'rourke, Eyleen J.; Orozco, Helena; Ortega, Angel L.; Ortona, Elena; Osellame, Laura D.; Oshima, Junko; Oshima, Shigeru; Osiewacz, Heinz D.; Otomo, Takanobu; Otsu, Kinya; Ou, Jing Hsiung James; Outeiro, Tiago F.; Ouyang, Dong Yun; Ouyang, Hongjiao; Overholtzer, Michael; Ozbun, Michelle A.; Ozdinler, P. 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SCOPUS:85054826264

ISSN: 1554-8627

CID: 5487622

Neuro-degenerative diseases. 2016:16(1-2):34-8.DOI: 10.1159/000440842

Tau Immunotherapy

Sigurdsson, Einar M

In recent years, tau immunotherapy has advanced from proof-of-concept studies [Sigurdsson EM, NIH R01AG020197, 2001; Asuni AA, et al: J Neurosci 2007;27:9115-9129], which have now been confirmed and extended by us and others. Phase I clinical trials on active and passive tau immunizations are being conducted, with several additional passive tau antibody trials likely to be initiated in the near future for Alzheimer's disease and other tauopathies. Because tau pathology correlates better with the degree of dementia than amyloid-beta (Abeta) pathology, greater clinical efficacy may be achieved by clearing tau than Abeta aggregates in the later stages of the disease, when cognitive impairments become evident. Substantial insight has now been obtained regarding which epitopes to target, mechanism of action and potential toxicity, but much remains to be clarified. All of these factors likely depend on the model/disease or stage of pathology and the immunogen/antibody. Interestingly, tau antibodies interact with the protein both extra- and intracellularly, but the importance of each site for tau clearance is not well defined. Some antibodies are readily taken up into neurons, whereas others are not. It can be argued that extracellular clearance may be safer but less efficacious than intraneuronal clearance and/or sequestration to prevent secretion and further spread of tau pathology. Development of therapeutic tau antibodies has led to antibody-derived imaging probes, which are more specific than the dye-based compounds that are already in clinical trials. Such specificity may give valuable information on the pathological tau epitope profile, which could then guide the selection of therapeutic antibodies for maximal efficacy and safety. Hopefully, tau immunotherapy will be effective in clinical trials, and further advanced by mechanistic clarification in experimental models with insights from biomarkers and postmortem analyses of clinical subjects.

PMCID:4777344

PMID: 26551002

ISSN: 1660-2862

CID: 1834672

Autophagy. 2016:12(1):1-222.DOI: 10.1080/15548627.2015.1100356

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) [Guideline]

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Burke, Robert E; Burmeister, Margit; Butikofer, Peter; Caberlotto, Laura; Cadwell, Ken; Cahova, Monika; Cai, Dongsheng; Cai, Jingjing; Cai, Qian; Calatayud, Sara; Camougrand, Nadine; Campanella, Michelangelo; Campbell, Grant R; Campbell, Matthew; Campello, Silvia; Candau, Robin; Caniggia, Isabella; Cantoni, Lavinia; Cao, Lizhi; Caplan, Allan B; Caraglia, Michele; Cardinali, Claudio; Cardoso, Sandra Morais; Carew, Jennifer S; Carleton, Laura A; Carlin, Cathleen R; Carloni, Silvia; Carlsson, Sven R; Carmona-Gutierrez, Didac; Carneiro, Leticia Am; Carnevali, Oliana; Carra, Serena; Carrier, Alice; Carroll, Bernadette; Casas, Caty; Casas, Josefina; Cassinelli, Giuliana; Castets, Perrine; Castro-Obregon, Susana; Cavallini, Gabriella; Ceccherini, Isabella; Cecconi, Francesco; Cederbaum, Arthur I; Cena, Valentin; Cenci, Simone; Cerella, Claudia; Cervia, Davide; Cetrullo, Silvia; Chaachouay, Hassan; Chae, Han-Jung; Chagin, Andrei S; Chai, Chee-Yin; Chakrabarti, Gopal; Chamilos, Georgios; Chan, Edmond Yw; Chan, Matthew Tv; Chandra, Dhyan; Chandra, Pallavi; Chang, Chih-Peng; Chang, Raymond Chuen-Chung; Chang, Ta Yuan; Chatham, John C; Chatterjee, Saurabh; Chauhan, Santosh; Che, Yongsheng; Cheetham, Michael E; Cheluvappa, Rajkumar; Chen, Chun-Jung; Chen, Gang; Chen, Guang-Chao; Chen, Guoqiang; Chen, Hongzhuan; Chen, Jeff W; Chen, Jian-Kang; Chen, Min; Chen, Mingzhou; Chen, Peiwen; Chen, Qi; Chen, Quan; Chen, Shang-Der; Chen, Si; Chen, Steve S-L; Chen, Wei; Chen, Wei-Jung; Chen, Wen Qiang; Chen, Wenli; Chen, Xiangmei; Chen, Yau-Hung; Chen, Ye-Guang; Chen, Yin; Chen, Yingyu; Chen, Yongshun; Chen, Yu-Jen; Chen, Yue-Qin; Chen, Yujie; Chen, Zhen; Chen, Zhong; Cheng, Alan; Cheng, Christopher Hk; Cheng, Hua; Cheong, Heesun; Cherry, Sara; Chesney, Jason; Cheung, Chun Hei Antonio; Chevet, Eric; Chi, Hsiang Cheng; Chi, Sung-Gil; Chiacchiera, Fulvio; Chiang, Hui-Ling; Chiarelli, Roberto; Chiariello, Mario; Chieppa, Marcello; Chin, Lih-Shen; Chiong, Mario; Chiu, Gigi Nc; Cho, Dong-Hyung; Cho, Ssang-Goo; Cho, William C; Cho, Yong-Yeon; Cho, Young-Seok; Choi, Augustine Mk; Choi, Eui-Ju; Choi, Eun-Kyoung; Choi, Jayoung; Choi, Mary E; Choi, Seung-Il; Chou, Tsui-Fen; Chouaib, Salem; Choubey, Divaker; Choubey, Vinay; Chow, Kuan-Chih; Chowdhury, Kamal; Chu, Charleen T; Chuang, Tsung-Hsien; Chun, Taehoon; Chung, Hyewon; Chung, Taijoon; Chung, Yuen-Li; Chwae, Yong-Joon; Cianfanelli, Valentina; Ciarcia, Roberto; Ciechomska, Iwona A; Ciriolo, Maria Rosa; Cirone, Mara; Claerhout, Sofie; Clague, Michael J; Claria, Joan; Clarke, Peter Gh; Clarke, Robert; Clementi, Emilio; Cleyrat, Cedric; Cnop, Miriam; Coccia, Eliana M; Cocco, Tiziana; Codogno, Patrice; Coers, Jorn; Cohen, Ezra Ew; Colecchia, David; Coletto, Luisa; Coll, Nuria S; Colucci-Guyon, Emma; Comincini, Sergio; Condello, Maria; Cook, Katherine L; Coombs, Graham H; Cooper, Cynthia D; Cooper, J Mark; Coppens, Isabelle; Corasaniti, Maria Tiziana; Corazzari, Marco; Corbalan, Ramon; Corcelle-Termeau, Elisabeth; Cordero, Mario D; Corral-Ramos, Cristina; Corti, Olga; Cossarizza, Andrea; Costelli, Paola; Costes, Safia; Cotman, Susan L; Coto-Montes, Ana; Cottet, Sandra; Couve, Eduardo; Covey, Lori R; Cowart, L Ashley; Cox, Jeffery S; Coxon, Fraser P; Coyne, Carolyn B; Cragg, Mark S; Craven, Rolf J; Crepaldi, Tiziana; Crespo, Jose L; Criollo, Alfredo; Crippa, Valeria; Cruz, Maria Teresa; Cuervo, Ana Maria; Cuezva, Jose M; Cui, Taixing; Cutillas, Pedro R; Czaja, Mark J; Czyzyk-Krzeska, Maria F; Dagda, Ruben K; Dahmen, Uta; Dai, Chunsun; Dai, Wenjie; Dai, Yun; Dalby, Kevin N; Dalla Valle, Luisa; Dalmasso, Guillaume; D'Amelio, Marcello; Damme, Markus; Darfeuille-Michaud, Arlette; Dargemont, Catherine; Darley-Usmar, Victor M; Dasarathy, Srinivasan; Dasgupta, Biplab; Dash, Srikanta; Dass, Crispin R; Davey, Hazel Marie; Davids, Lester M; Davila, David; Davis, Roger J; Dawson, Ted M; Dawson, Valina L; Daza, Paula; de Belleroche, Jackie; de Figueiredo, Paul; de Figueiredo, Regina Celia Bressan Queiroz; de la Fuente, Jose; De Martino, Luisa; De Matteis, Antonella; De Meyer, Guido Ry; De Milito, Angelo; De Santi, Mauro; de Souza, Wanderley; De Tata, Vincenzo; De Zio, Daniela; Debnath, Jayanta; Dechant, Reinhard; Decuypere, Jean-Paul; Deegan, Shane; Dehay, Benjamin; Del Bello, Barbara; Del Re, Dominic P; Delage-Mourroux, Regis; Delbridge, Lea Md; Deldicque, Louise; Delorme-Axford, Elizabeth; Deng, Yizhen; Dengjel, Joern; Denizot, Melanie; Dent, Paul; Der, Channing J; Deretic, Vojo; Derrien, Benoit; Deutsch, Eric; Devarenne, Timothy P; Devenish, Rodney J; Di Bartolomeo, Sabrina; Di Daniele, Nicola; Di Domenico, Fabio; Di Nardo, Alessia; Di Paola, Simone; Di Pietro, Antonio; Di Renzo, Livia; DiAntonio, Aaron; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T; Diaz-Nido, Javier; Dickey, Chad A; Dickson, Robert C; Diederich, Marc; Digard, Paul; Dikic, Ivan; Dinesh-Kumar, Savithrama P; Ding, Chan; Ding, Wen-Xing; Ding, Zufeng; Dini, Luciana; Distler, Jorg Hw; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dmytruk, Kostyantyn; Dobson, Renwick Cj; Doetsch, Volker; Dokladny, Karol; Dokudovskaya, Svetlana; Donadelli, Massimo; Dong, X Charlie; Dong, Xiaonan; Dong, Zheng; Donohue, Terrence M Jr; Doran, Kelly S; D'Orazi, Gabriella; Dorn, Gerald W 2nd; Dosenko, Victor; Dridi, Sami; Drucker, Liat; Du, Jie; Du, Li-Lin; Du, Lihuan; du Toit, Andre; Dua, Priyamvada; Duan, Lei; Duann, Pu; Dubey, Vikash Kumar; Duchen, Michael R; Duchosal, Michel A; Duez, Helene; Dugail, Isabelle; Dumit, Veronica I; Duncan, Mara C; Dunlop, Elaine A; Dunn, William A Jr; Dupont, Nicolas; Dupuis, Luc; Duran, Raul V; Durcan, Thomas M; Duvezin-Caubet, Stephane; Duvvuri, Umamaheswar; Eapen, Vinay; Ebrahimi-Fakhari, Darius; Echard, Arnaud; Eckhart, Leopold; Edelstein, Charles L; Edinger, Aimee L; Eichinger, Ludwig; Eisenberg, Tobias; Eisenberg-Lerner, Avital; Eissa, N Tony; El-Deiry, Wafik S; El-Khoury, Victoria; Elazar, Zvulun; Eldar-Finkelman, Hagit; Elliott, Chris Jh; Emanuele, Enzo; Emmenegger, Urban; Engedal, Nikolai; Engelbrecht, Anna-Mart; Engelender, Simone; Enserink, Jorrit M; Erdmann, Ralf; Erenpreisa, Jekaterina; Eri, Rajaraman; Eriksen, Jason L; Erman, Andreja; Escalante, Ricardo; Eskelinen, Eeva-Liisa; Espert, Lucile; Esteban-Martinez, Lorena; Evans, Thomas J; Fabri, Mario; Fabrias, Gemma; Fabrizi, Cinzia; Facchiano, Antonio; Faergeman, Nils J; Faggioni, Alberto; Fairlie, W Douglas; Fan, Chunhai; Fan, Daping; Fan, Jie; Fang, Shengyun; Fanto, Manolis; Fanzani, Alessandro; Farkas, Thomas; Faure, Mathias; Favier, Francois B; Fearnhead, Howard; Federici, Massimo; Fei, Erkang; Felizardo, Tania C; Feng, Hua; Feng, Yibin; Feng, Yuchen; Ferguson, Thomas A; Fernandez, Alvaro F; Fernandez-Barrena, Maite G; Fernandez-Checa, Jose C; Fernandez-Lopez, Arsenio; Fernandez-Zapico, Martin E; Feron, Olivier; Ferraro, Elisabetta; Ferreira-Halder, Carmen Verissima; Fesus, Laszlo; Feuer, Ralph; Fiesel, Fabienne C; Filippi-Chiela, Eduardo C; Filomeni, Giuseppe; Fimia, Gian Maria; Fingert, John H; Finkbeiner, Steven; Finkel, Toren; Fiorito, Filomena; Fisher, Paul B; Flajolet, Marc; Flamigni, Flavio; Florey, Oliver; Florio, Salvatore; Floto, R Andres; Folini, Marco; Follo, Carlo; Fon, Edward A; Fornai, Francesco; Fortunato, Franco; Fraldi, Alessandro; Franco, Rodrigo; Francois, Arnaud; Francois, Aurelie; Frankel, Lisa B; Fraser, Iain Dc; Frey, Norbert; Freyssenet, Damien G; Frezza, Christian; Friedman, Scott L; Frigo, Daniel E; Fu, Dongxu; Fuentes, Jose M; Fueyo, Juan; Fujitani, Yoshio; Fujiwara, Yuuki; Fujiya, Mikihiro; Fukuda, Mitsunori; Fulda, Simone; Fusco, Carmela; Gabryel, Bozena; Gaestel, Matthias; Gailly, Philippe; Gajewska, Malgorzata; Galadari, Sehamuddin; Galili, Gad; Galindo, Inmaculada; Galindo, Maria F; Galliciotti, Giovanna; Galluzzi, Lorenzo; Galluzzi, Luca; Galy, Vincent; Gammoh, Noor; Gandy, Sam; Ganesan, Anand K; Ganesan, Swamynathan; Ganley, Ian G; Gannage, Monique; Gao, Fen-Biao; Gao, Feng; Gao, Jian-Xin; Garcia Nannig, Lorena; Garcia Vescovi, Eleonora; Garcia-Macia, Marina; Garcia-Ruiz, Carmen; Garg, Abhishek D; Garg, Pramod Kumar; Gargini, Ricardo; Gassen, Nils Christian; Gatica, Damian; Gatti, Evelina; Gavard, Julie; Gavathiotis, Evripidis; Ge, Liang; Ge, Pengfei; Ge, Shengfang; Gean, Po-Wu; Gelmetti, Vania; Genazzani, Armando A; Geng, Jiefei; Genschik, Pascal; Gerner, Lisa; Gestwicki, Jason E; Gewirtz, David A; Ghavami, Saeid; Ghigo, Eric; Ghosh, Debabrata; Giammarioli, Anna Maria; Giampieri, Francesca; Giampietri, Claudia; Giatromanolaki, Alexandra; Gibbings, Derrick J; Gibellini, Lara; Gibson, Spencer B; Ginet, Vanessa; Giordano, Antonio; Giorgini, Flaviano; Giovannetti, Elisa; Girardin, Stephen E; Gispert, Suzana; Giuliano, Sandy; Gladson, Candece L; Glavic, Alvaro; Gleave, Martin; Godefroy, Nelly; Gogal, Robert M Jr; Gokulan, Kuppan; Goldman, Gustavo H; Goletti, Delia; Goligorsky, Michael S; Gomes, Aldrin V; Gomes, Ligia C; Gomez, Hernando; Gomez-Manzano, Candelaria; Gomez-Sanchez, Ruben; Goncalves, Dawit Ap; Goncu, Ebru; Gong, Qingqiu; Gongora, Celine; Gonzalez, Carlos B; Gonzalez-Alegre, Pedro; Gonzalez-Cabo, Pilar; Gonzalez-Polo, Rosa Ana; Goping, Ing Swie; Gorbea, Carlos; Gorbunov, Nikolai V; Goring, Daphne R; Gorman, Adrienne M; Gorski, Sharon M; Goruppi, Sandro; Goto-Yamada, Shino; Gotor, Cecilia; Gottlieb, Roberta A; Gozes, Illana; Gozuacik, Devrim; Graba, Yacine; Graef, Martin; Granato, Giovanna E; Grant, Gary Dean; Grant, Steven; Gravina, Giovanni Luca; Green, Douglas R; Greenhough, Alexander; Greenwood, Michael T; Grimaldi, Benedetto; Gros, Frederic; Grose, Charles; Groulx, Jean-Francois; Gruber, Florian; Grumati, Paolo; Grune, Tilman; Guan, Jun-Lin; Guan, Kun-Liang; Guerra, Barbara; Guillen, Carlos; Gulshan, Kailash; Gunst, Jan; Guo, Chuanyong; Guo, Lei; Guo, Ming; Guo, Wenjie; Guo, Xu-Guang; Gust, Andrea A; Gustafsson, Asa B; Gutierrez, Elaine; Gutierrez, Maximiliano G; Gwak, Ho-Shin; Haas, Albert; Haber, James E; Hadano, Shinji; Hagedorn, Monica; Hahn, David R; Halayko, Andrew J; Hamacher-Brady, Anne; Hamada, Kozo; Hamai, Ahmed; Hamann, Andrea; Hamasaki, Maho; Hamer, Isabelle; Hamid, Qutayba; Hammond, Ester M; Han, Feng; Han, Weidong; Handa, James T; Hanover, John A; Hansen, Malene; Harada, Masaru; Harhaji-Trajkovic, Ljubica; Harper, J Wade; Harrath, Abdel Halim; Harris, Adrian L; Harris, James; Hasler, Udo; Hasselblatt, Peter; Hasui, Kazuhisa; Hawley, Robert G; Hawley, Teresa S; He, Congcong; He, Cynthia Y; He, Fengtian; He, Gu; He, Rong-Rong; He, Xian-Hui; He, You-Wen; He, Yu-Ying; Heath, Joan K; Hebert, Marie-Josee; Heinzen, Robert A; Helgason, Gudmundur Vignir; Hensel, Michael; Henske, Elizabeth P; Her, Chengtao; Herman, Paul K; Hernandez, Agustin; Hernandez, Carlos; Hernandez-Tiedra, Sonia; Hetz, Claudio; Hiesinger, P Robin; Higaki, Katsumi; Hilfiker, Sabine; Hill, Bradford G; Hill, Joseph A; Hill, William D; Hino, Keisuke; Hofius, Daniel; Hofman, Paul; Hoglinger, Gunter U; Hohfeld, Jorg; Holz, Marina K; Hong, Yonggeun; Hood, David A; Hoozemans, Jeroen Jm; Hoppe, Thorsten; Hsu, Chin; Hsu, Chin-Yuan; Hsu, Li-Chung; Hu, Dong; Hu, Guochang; Hu, Hong-Ming; Hu, Hongbo; Hu, Ming Chang; Hu, Yu-Chen; Hu, Zhuo-Wei; Hua, Fang; Hua, Ya; Huang, Canhua; Huang, Huey-Lan; Huang, Kuo-How; Huang, Kuo-Yang; Huang, Shile; Huang, Shiqian; Huang, Wei-Pang; Huang, Yi-Ran; Huang, Yong; Huang, Yunfei; Huber, Tobias B; Huebbe, Patricia; Huh, Won-Ki; Hulmi, Juha J; Hur, Gang Min; Hurley, James H; Husak, Zvenyslava; Hussain, Sabah Na; Hussain, Salik; Hwang, Jung Jin; Hwang, Seungmin; Hwang, Thomas Is; Ichihara, Atsuhiro; Imai, Yuzuru; Imbriano, Carol; Inomata, Megumi; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L; Iozzo, Renato V; Ip, Nancy Y; Irazoqui, Javier E; Iribarren, Pablo; Isaka, Yoshitaka; Isakovic, Aleksandra J; Ischiropoulos, Harry; Isenberg, Jeffrey S; Ishaq, Mohammad; Ishida, Hiroyuki; Ishii, Isao; Ishmael, Jane E; Isidoro, Ciro; Isobe, Ken-Ichi; Isono, Erika; Issazadeh-Navikas, Shohreh; Itahana, Koji; Itakura, Eisuke; Ivanov, Andrei I; Iyer, Anand Krishnan V; Izquierdo, Jose M; Izumi, Yotaro; Izzo, Valentina; Jaattela, Marja; Jaber, Nadia; Jackson, Daniel John; Jackson, William T; Jacob, Tony George; Jacques, Thomas S; Jagannath, Chinnaswamy; Jain, Ashish; Jana, Nihar Ranjan; Jang, Byoung Kuk; Jani, Alkesh; Janji, Bassam; Jannig, Paulo Roberto; Jansson, Patric J; Jean, Steve; Jendrach, Marina; Jeon, Ju-Hong; Jessen, Niels; Jeung, Eui-Bae; Jia, Kailiang; Jia, Lijun; Jiang, Hong; Jiang, Hongchi; Jiang, Liwen; Jiang, Teng; Jiang, Xiaoyan; Jiang, Xuejun; Jiang, Xuejun; Jiang, Ying; Jiang, Yongjun; Jimenez, Alberto; Jin, Cheng; Jin, Hongchuan; Jin, Lei; Jin, Meiyan; Jin, Shengkan; Jinwal, Umesh Kumar; Jo, Eun-Kyeong; Johansen, Terje; Johnson, Daniel E; Johnson, Gail Vw; Johnson, James D; Jonasch, Eric; Jones, Chris; Joosten, Leo Ab; Jordan, Joaquin; Joseph, Anna-Maria; Joseph, Bertrand; Joubert, Annie M; Ju, Dianwen; Ju, Jingfang; Juan, Hsueh-Fen; Juenemann, Katrin; Juhasz, Gabor; Jung, Hye Seung; Jung, Jae U; Jung, Yong-Keun; Jungbluth, Heinz; Justice, Matthew J; Jutten, Barry; Kaakoush, Nadeem O; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kaeffer, Bertrand; Kagedal, Katarina; Kahana, Alon; Kajimura, Shingo; Kakhlon, Or; Kalia, Manjula; Kalvakolanu, Dhan V; Kamada, Yoshiaki; Kambas, Konstantinos; Kaminskyy, Vitaliy O; Kampinga, Harm H; Kandouz, Mustapha; Kang, Chanhee; Kang, Rui; Kang, Tae-Cheon; Kanki, Tomotake; Kanneganti, Thirumala-Devi; Kanno, Haruo; Kanthasamy, Anumantha G; Kantorow, Marc; Kaparakis-Liaskos, Maria; Kapuy, Orsolya; Karantza, Vassiliki; Karim, Md Razaul; Karmakar, Parimal; Kaser, Arthur; Kaushik, Susmita; Kawula, Thomas; Kaynar, A Murat; Ke, Po-Yuan; Ke, Zun-Ji; Kehrl, John H; Keller, Kate E; Kemper, Jongsook Kim; Kenworthy, Anne K; Kepp, Oliver; Kern, Andreas; Kesari, Santosh; Kessel, David; Ketteler, Robin; Kettelhut, Isis do Carmo; Khambu, Bilon; Khan, Muzamil Majid; Khandelwal, Vinoth Km; Khare, Sangeeta; Kiang, Juliann G; Kiger, Amy A; Kihara, Akio; Kim, Arianna L; Kim, Cheol Hyeon; Kim, Deok Ryong; Kim, Do-Hyung; Kim, Eung Kweon; Kim, Hye Young; Kim, Hyung-Ryong; Kim, Jae-Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, Jin Hyoung; Kim, Kwang Woon; Kim, Michael D; Kim, Moon-Moo; Kim, Peter K; Kim, Seong Who; Kim, Soo-Youl; Kim, Yong-Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C; Kimura, Tomonori; King, Jason S; Kirkegaard, Karla; Kirkin, Vladimir; Kirshenbaum, Lorrie A; Kishi, Shuji; Kitajima, Yasuo; Kitamoto, Katsuhiko; Kitaoka, Yasushi; Kitazato, Kaio; Kley, Rudolf A; Klimecki, Walter T; Klinkenberg, Michael; Klucken, Jochen; Knaevelsrud, Helene; Knecht, Erwin; Knuppertz, Laura; Ko, Jiunn-Liang; Kobayashi, Satoru; Koch, Jan C; Koechlin-Ramonatxo, Christelle; Koenig, Ulrich; Koh, Young Ho; Kohler, Katja; Kohlwein, Sepp D; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Dexin; Kong, Hee Jeong; Konstantakou, Eumorphia G; Kopp, Benjamin T; Korcsmaros, Tamas; Korhonen, Laura; Korolchuk, Viktor I; Koshkina, Nadya V; Kou, Yanjun; Koukourakis, Michael I; Koumenis, Constantinos; Kovacs, Attila L; Kovacs, Tibor; Kovacs, Werner J; Koya, Daisuke; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kravic-Stevovic, Tamara; Krek, Wilhelm; Kretz-Remy, Carole; Krick, Roswitha; Krishnamurthy, Malathi; Kriston-Vizi, Janos; Kroemer, Guido; Kruer, Michael C; Kruger, Rejko; Ktistakis, Nicholas T; Kuchitsu, Kazuyuki; Kuhn, Christian; Kumar, Addanki Pratap; Kumar, Anuj; Kumar, Ashok; Kumar, Deepak; Kumar, Dhiraj; Kumar, Rakesh; Kumar, Sharad; Kundu, Mondira; Kung, Hsing-Jien; Kuno, Atsushi; Kuo, Sheng-Han; Kuret, Jeff; Kurz, Tino; Kwok, Terry; Kwon, Taeg Kyu; Kwon, Yong Tae; Kyrmizi, Irene; La Spada, Albert R; Lafont, Frank; Lahm, Tim; Lakkaraju, Aparna; Lam, Truong; Lamark, Trond; Lancel, Steve; Landowski, Terry H; Lane, Darius Jr; Lane, Jon D; Lanzi, Cinzia; Lapaquette, Pierre; Lapierre, Louis R; Laporte, Jocelyn; Laukkarinen, Johanna; Laurie, Gordon W; Lavandero, Sergio; Lavie, Lena; LaVoie, Matthew J; Law, Betty Yuen Kwan; Law, Helen Ka-Wai; Law, Kelsey B; Layfield, Robert; Lazo, Pedro A; Le Cam, Laurent; Le Roch, Karine G; Le Stunff, Herve; Leardkamolkarn, Vijittra; Lecuit, Marc; Lee, Byung-Hoon; Lee, Che-Hsin; Lee, Erinna F; Lee, Gyun Min; Lee, He-Jin; Lee, Hsinyu; Lee, Jae Keun; Lee, Jongdae; Lee, Ju-Hyun; Lee, Jun Hee; Lee, Michael; Lee, Myung-Shik; Lee, Patty J; Lee, Sam W; Lee, Seung-Jae; Lee, Shiow-Ju; Lee, Stella Y; Lee, Sug Hyung; Lee, Sung Sik; Lee, Sung-Joon; Lee, Sunhee; Lee, Ying-Ray; Lee, Yong J; Lee, Young H; Leeuwenburgh, Christiaan; Lefort, Sylvain; Legouis, Renaud; Lei, Jinzhi; Lei, Qun-Ying; Leib, David A; Leibowitz, Gil; Lekli, Istvan; Lemaire, Stephane D; Lemasters, John J; Lemberg, Marius K; Lemoine, Antoinette; Leng, Shuilong; Lenz, Guido; Lenzi, Paola; Lerman, Lilach O; Lettieri Barbato, Daniele; Leu, Julia I-Ju; Leung, Hing Y; Levine, Beth; Lewis, Patrick A; Lezoualc'h, Frank; Li, Chi; Li, Faqiang; Li, Feng-Jun; Li, Jun; Li, Ke; Li, Lian; Li, Min; Li, Min; Li, Qiang; Li, Rui; Li, Sheng; Li, Wei; Li, Wei; Li, Xiaotao; Li, Yumin; Lian, Jiqin; Liang, Chengyu; Liang, Qiangrong; Liao, Yulin; Liberal, Joana; Liberski, Pawel P; Lie, Pearl; Lieberman, Andrew P; Lim, Hyunjung Jade; Lim, Kah-Leong; Lim, Kyu; Lima, Raquel T; Lin, Chang-Shen; Lin, Chiou-Feng; Lin, Fang; Lin, Fangming; Lin, Fu-Cheng; Lin, Kui; Lin, Kwang-Huei; Lin, Pei-Hui; Lin, Tianwei; Lin, Wan-Wan; Lin, Yee-Shin; Lin, Yong; Linden, Rafael; Lindholm, Dan; Lindqvist, Lisa M; Lingor, Paul; Linkermann, Andreas; Liotta, Lance A; Lipinski, Marta M; Lira, Vitor A; Lisanti, Michael P; Liton, Paloma B; Liu, Bo; Liu, Chong; Liu, Chun-Feng; Liu, Fei; Liu, Hung-Jen; Liu, Jianxun; Liu, Jing-Jing; Liu, Jing-Lan; Liu, Ke; Liu, Leyuan; Liu, Liang; Liu, Quentin; Liu, Rong-Yu; Liu, Shiming; Liu, Shuwen; Liu, Wei; Liu, Xian-De; Liu, Xiangguo; Liu, Xiao-Hong; Liu, Xinfeng; Liu, Xu; Liu, Xueqin; Liu, Yang; Liu, Yule; Liu, Zexian; Liu, Zhe; Liuzzi, Juan P; Lizard, Gerard; Ljujic, Mila; Lodhi, Irfan J; Logue, Susan E; Lokeshwar, Bal L; Long, Yun Chau; Lonial, Sagar; Loos, Benjamin; Lopez-Otin, Carlos; Lopez-Vicario, Cristina; Lorente, Mar; Lorenzi, Philip L; Lorincz, Peter; Los, Marek; Lotze, Michael T; Lovat, Penny E; Lu, Binfeng; Lu, Bo; Lu, Jiahong; Lu, Qing; Lu, She-Min; Lu, Shuyan; Lu, Yingying; Luciano, Frederic; Luckhart, Shirley; Lucocq, John Milton; Ludovico, Paula; Lugea, Aurelia; Lukacs, Nicholas W; Lum, Julian J; Lund, Anders H; Luo, Honglin; Luo, Jia; Luo, Shouqing; Luparello, Claudio; Lyons, Timothy; Ma, Jianjie; Ma, Yi; Ma, Yong; Ma, Zhenyi; Machado, Juliano; Machado-Santelli, Glaucia M; Macian, Fernando; MacIntosh, Gustavo C; MacKeigan, Jeffrey P; Macleod, Kay F; MacMicking, John D; MacMillan-Crow, Lee Ann; Madeo, Frank; Madesh, Muniswamy; Madrigal-Matute, Julio; Maeda, Akiko; Maeda, Tatsuya; Maegawa, Gustavo; Maellaro, Emilia; Maes, Hannelore; Magarinos, Marta; Maiese, Kenneth; Maiti, Tapas K; Maiuri, Luigi; Maiuri, Maria Chiara; Maki, Carl G; Malli, Roland; Malorni, Walter; Maloyan, Alina; Mami-Chouaib, Fathia; Man, Na; Mancias, Joseph D; Mandelkow, Eva-Maria; Mandell, Michael A; Manfredi, Angelo A; Manie, Serge N; Manzoni, Claudia; Mao, Kai; Mao, Zixu; Mao, Zong-Wan; Marambaud, Philippe; Marconi, Anna Maria; Marelja, Zvonimir; Marfe, Gabriella; Margeta, Marta; Margittai, Eva; Mari, Muriel; Mariani, Francesca V; Marin, Concepcio; Marinelli, Sara; Marino, Guillermo; Markovic, Ivanka; Marquez, Rebecca; Martelli, Alberto M; Martens, Sascha; Martin, Katie R; Martin, Seamus J; Martin, Shaun; Martin-Acebes, Miguel A; Martin-Sanz, Paloma; Martinand-Mari, Camille; Martinet, Wim; Martinez, Jennifer; Martinez-Lopez, Nuria; Martinez-Outschoorn, Ubaldo; Martinez-Velazquez, Moises; Martinez-Vicente, Marta; Martins, Waleska Kerllen; Mashima, Hirosato; Mastrianni, James A; Matarese, Giuseppe; Matarrese, Paola; Mateo, Roberto; Matoba, Satoaki; Matsumoto, Naomichi; Matsushita, Takehiko; Matsuura, Akira; Matsuzawa, Takeshi; Mattson, Mark P; Matus, Soledad; Maugeri, Norma; Mauvezin, Caroline; Mayer, Andreas; Maysinger, Dusica; Mazzolini, Guillermo D; McBrayer, Mary Kate; McCall, Kimberly; McCormick, Craig; McInerney, Gerald M; McIver, Skye C; McKenna, Sharon; McMahon, John J; McNeish, Iain A; Mechta-Grigoriou, Fatima; Medema, Jan Paul; Medina, Diego L; Megyeri, Klara; Mehrpour, Maryam; Mehta, Jawahar L; Mei, Yide; Meier, Ute-Christiane; Meijer, Alfred J; Melendez, Alicia; Melino, Gerry; Melino, Sonia; de Melo, Edesio Jose Tenorio; Mena, Maria A; Meneghini, Marc D; Menendez, Javier A; Menezes, Regina; Meng, Liesu; Meng, Ling-Hua; Meng, Songshu; Menghini, Rossella; Menko, A Sue; Menna-Barreto, Rubem Fs; Menon, Manoj B; Meraz-Rios, Marco A; Merla, Giuseppe; Merlini, Luciano; Merlot, Angelica M; Meryk, Andreas; Meschini, Stefania; Meyer, Joel N; Mi, Man-Tian; Miao, Chao-Yu; Micale, Lucia; Michaeli, Simon; Michiels, Carine; Migliaccio, Anna Rita; Mihailidou, Anastasia Susie; Mijaljica, Dalibor; Mikoshiba, Katsuhiko; Milan, Enrico; Miller-Fleming, Leonor; Mills, Gordon B; Mills, Ian G; Minakaki, Georgia; Minassian, Berge A; Ming, Xiu-Fen; Minibayeva, Farida; Minina, Elena A; Mintern, Justine D; Minucci, Saverio; Miranda-Vizuete, Antonio; Mitchell, Claire H; Miyamoto, Shigeki; Miyazawa, Keisuke; Mizushima, Noboru; Mnich, Katarzyna; Mograbi, Baharia; Mohseni, Simin; Moita, Luis Ferreira; Molinari, Marco; Molinari, Maurizio; Moller, Andreas Buch; Mollereau, Bertrand; Mollinedo, Faustino; Mongillo, Marco; Monick, Martha M; Montagnaro, Serena; Montell, Craig; Moore, Darren J; Moore, Michael N; Mora-Rodriguez, Rodrigo; Moreira, Paula I; Morel, Etienne; Morelli, Maria Beatrice; Moreno, Sandra; Morgan, Michael J; Moris, Arnaud; Moriyasu, Yuji; Morrison, Janna L; Morrison, Lynda A; Morselli, Eugenia; Moscat, Jorge; Moseley, Pope L; Mostowy, Serge; Motori, Elisa; Mottet, Denis; Mottram, Jeremy C; Moussa, Charbel E-H; Mpakou, Vassiliki E; Mukhtar, Hasan; Mulcahy Levy, Jean M; Muller, Sylviane; Munoz-Moreno, Raquel; Munoz-Pinedo, Cristina; Munz, Christian; Murphy, Maureen E; Murray, James T; Murthy, Aditya; Mysorekar, Indira U; Nabi, Ivan R; Nabissi, Massimo; Nader, Gustavo A; Nagahara, Yukitoshi; Nagai, Yoshitaka; Nagata, Kazuhiro; Nagelkerke, Anika; Nagy, Peter; Naidu, Samisubbu R; Nair, Sreejayan; Nakano, Hiroyasu; Nakatogawa, Hitoshi; Nanjundan, Meera; Napolitano, Gennaro; Naqvi, Naweed I; Nardacci, Roberta; Narendra, Derek P; Narita, Masashi; Nascimbeni, Anna Chiara; Natarajan, Ramesh; Navegantes, Luiz C; Nawrocki, Steffan T; Nazarko, Taras Y; Nazarko, Volodymyr Y; Neill, Thomas; Neri, Luca M; Netea, Mihai G; Netea-Maier, Romana T; Neves, Bruno M; Ney, Paul A; Nezis, Ioannis P; Nguyen, Hang Tt; Nguyen, Huu Phuc; Nicot, Anne-Sophie; Nilsen, Hilde; Nilsson, Per; Nishimura, Mikio; Nishino, Ichizo; Niso-Santano, Mireia; Niu, Hua; Nixon, Ralph A; Njar, Vincent Co; Noda, Takeshi; Noegel, Angelika A; Nolte, Elsie Magdalena; Norberg, Erik; Norga, Koenraad K; Noureini, Sakineh Kazemi; Notomi, Shoji; Notterpek, Lucia; Nowikovsky, Karin; Nukina, Nobuyuki; Nurnberger, Thorsten; O'Donnell, Valerie B; O'Donovan, Tracey; O'Dwyer, Peter J; Oehme, Ina; Oeste, Clara L; Ogawa, Michinaga; Ogretmen, Besim; Ogura, Yuji; Oh, Young J; Ohmuraya, Masaki; Ohshima, Takayuki; Ojha, Rani; Okamoto, Koji; Okazaki, Toshiro; Oliver, F Javier; Ollinger, Karin; Olsson, Stefan; Orban, Daniel P; Ordonez, Paulina; Orhon, Idil; Orosz, Laszlo; O'Rourke, Eyleen J; Orozco, Helena; Ortega, Angel L; Ortona, Elena; Osellame, Laura D; Oshima, Junko; Oshima, Shigeru; Osiewacz, Heinz D; Otomo, Takanobu; Otsu, Kinya; Ou, Jing-Hsiung James; Outeiro, Tiago F; Ouyang, Dong-Yun; Ouyang, Hongjiao; Overholtzer, Michael; Ozbun, Michelle A; Ozdinler, P Hande; Ozpolat, Bulent; Pacelli, Consiglia; Paganetti, Paolo; Page, Guylene; Pages, Gilles; Pagnini, Ugo; Pajak, Beata; Pak, Stephen C; Pakos-Zebrucka, Karolina; Pakpour, Nazzy; Palkova, Zdena; Palladino, Francesca; Pallauf, Kathrin; Pallet, Nicolas; Palmieri, Marta; Paludan, Soren R; Palumbo, Camilla; Palumbo, Silvia; Pampliega, Olatz; Pan, Hongming; Pan, Wei; Panaretakis, Theocharis; Pandey, Aseem; Pantazopoulou, Areti; Papackova, Zuzana; Papademetrio, Daniela L; Papassideri, Issidora; Papini, Alessio; Parajuli, Nirmala; Pardo, Julian; Parekh, Vrajesh V; Parenti, Giancarlo; Park, Jong-In; Park, Junsoo; Park, Ohkmae K; Parker, Roy; Parlato, Rosanna; Parys, Jan B; Parzych, Katherine R; Pasquet, Jean-Max; Pasquier, Benoit; Pasumarthi, Kishore Bs; Patschan, Daniel; Patterson, Cam; Pattingre, Sophie; Pattison, Scott; Pause, Arnim; Pavenstadt, Hermann; Pavone, Flaminia; Pedrozo, Zully; Pena, Fernando J; Penalva, Miguel A; Pende, Mario; Peng, Jianxin; Penna, Fabio; Penninger, Josef M; Pensalfini, Anna; Pepe, Salvatore; Pereira, Gustavo Js; Pereira, Paulo C; Perez-de la Cruz, Veronica; Perez-Perez, Maria Esther; Perez-Rodriguez, Diego; Perez-Sala, Dolores; Perier, Celine; Perl, Andras; Perlmutter, David H; Perrotta, Ida; Pervaiz, Shazib; Pesonen, Maija; Pessin, Jeffrey E; Peters, Godefridus J; Petersen, Morten; Petrache, Irina; Petrof, Basil J; Petrovski, Goran; Phang, James M; Piacentini, Mauro; Pierdominici, Marina; Pierre, Philippe; Pierrefite-Carle, Valerie; Pietrocola, Federico; Pimentel-Muinos, Felipe X; Pinar, Mario; Pineda, Benjamin; Pinkas-Kramarski, Ronit; Pinti, Marcello; Pinton, Paolo; Piperdi, Bilal; Piret, James M; Platanias, Leonidas C; Platta, Harald W; Plowey, Edward D; Poggeler, Stefanie; Poirot, Marc; Polcic, Peter; Poletti, Angelo; Poon, Audrey H; Popelka, Hana; Popova, Blagovesta; Poprawa, Izabela; Poulose, Shibu M; Poulton, Joanna; Powers, Scott K; Powers, Ted; Pozuelo-Rubio, Mercedes; Prak, Krisna; Prange, Reinhild; Prescott, Mark; Priault, Muriel; Prince, Sharon; Proia, Richard L; Proikas-Cezanne, Tassula; Prokisch, Holger; Promponas, Vasilis J; Przyklenk, Karin; Puertollano, Rosa; Pugazhenthi, Subbiah; Puglielli, Luigi; Pujol, Aurora; Puyal, Julien; Pyeon, Dohun; Qi, Xin; Qian, Wen-Bin; Qin, Zheng-Hong; Qiu, Yu; Qu, Ziwei; Quadrilatero, Joe; Quinn, Frederick; Raben, Nina; Rabinowich, Hannah; Radogna, Flavia; Ragusa, Michael J; Rahmani, Mohamed; Raina, Komal; Ramanadham, Sasanka; Ramesh, Rajagopal; Rami, Abdelhaq; Randall-Demllo, Sarron; Randow, Felix; Rao, Hai; Rao, V Ashutosh; Rasmussen, Blake B; Rasse, Tobias M; Ratovitski, Edward A; Rautou, Pierre-Emmanuel; Ray, Swapan K; Razani, Babak; Reed, Bruce H; Reggiori, Fulvio; Rehm, Markus; Reichert, Andreas S; Rein, Theo; Reiner, David J; Reits, Eric; Ren, Jun; Ren, Xingcong; Renna, Maurizio; Reusch, Jane Eb; Revuelta, Jose L; Reyes, Leticia; Rezaie, Alireza R; Richards, Robert I; Richardson, Des R; Richetta, Clemence; Riehle, Michael A; Rihn, Bertrand H; Rikihisa, Yasuko; Riley, Brigit E; Rimbach, Gerald; Rippo, Maria Rita; Ritis, Konstantinos; Rizzi, Federica; Rizzo, Elizete; Roach, Peter J; Robbins, Jeffrey; Roberge, Michel; Roca, Gabriela; Roccheri, Maria Carmela; Rocha, Sonia; Rodrigues, Cecilia Mp; Rodriguez, Clara I; de Cordoba, Santiago Rodriguez; Rodriguez-Muela, Natalia; Roelofs, Jeroen; Rogov, Vladimir V; Rohn, Troy T; Rohrer, Barbel; Romanelli, Davide; Romani, Luigina; Romano, Patricia Silvia; Roncero, M Isabel G; Rosa, Jose Luis; Rosello, Alicia; Rosen, Kirill V; Rosenstiel, Philip; Rost-Roszkowska, Magdalena; Roth, Kevin A; Roue, Gael; Rouis, Mustapha; Rouschop, Kasper M; Ruan, Daniel T; Ruano, Diego; Rubinsztein, David C; Rucker, Edmund B 3rd; Rudich, Assaf; Rudolf, Emil; Rudolf, Ruediger; Ruegg, Markus A; Ruiz-Roldan, Carmen; Ruparelia, Avnika Ashok; Rusmini, Paola; Russ, David W; Russo, Gian Luigi; Russo, Giuseppe; Russo, Rossella; Rusten, Tor Erik; Ryabovol, Victoria; Ryan, Kevin M; Ryter, Stefan W; Sabatini, David M; Sacher, Michael; Sachse, Carsten; Sack, Michael N; Sadoshima, Junichi; Saftig, Paul; Sagi-Eisenberg, Ronit; Sahni, Sumit; Saikumar, Pothana; Saito, Tsunenori; Saitoh, Tatsuya; Sakakura, Koichi; Sakoh-Nakatogawa, Machiko; Sakuraba, Yasuhito; Salazar-Roa, Maria; Salomoni, Paolo; Saluja, Ashok K; Salvaterra, Paul M; Salvioli, Rosa; Samali, Afshin; Sanchez, Anthony Mj; Sanchez-Alcazar, Jose A; Sanchez-Prieto, Ricardo; Sandri, Marco; Sanjuan, Miguel A; Santaguida, Stefano; Santambrogio, Laura; Santoni, Giorgio; Dos Santos, Claudia Nunes; Saran, Shweta; Sardiello, Marco; Sargent, Graeme; Sarkar, Pallabi; Sarkar, Sovan; Sarrias, Maria Rosa; Sarwal, Minnie M; Sasakawa, Chihiro; Sasaki, Motoko; Sass, Miklos; Sato, Ken; Sato, Miyuki; Satriano, Joseph; Savaraj, Niramol; Saveljeva, Svetlana; Schaefer, Liliana; Schaible, Ulrich E; Scharl, Michael; Schatzl, Hermann M; Schekman, Randy; Scheper, Wiep; Schiavi, Alfonso; Schipper, Hyman M; Schmeisser, Hana; Schmidt, Jens; Schmitz, Ingo; Schneider, Bianca E; Schneider, E Marion; Schneider, Jaime L; Schon, Eric A; Schonenberger, Miriam J; Schonthal, Axel H; Schorderet, Daniel F; Schroder, Bernd; Schuck, Sebastian; Schulze, Ryan J; Schwarten, Melanie; Schwarz, Thomas L; Sciarretta, Sebastiano; Scotto, Kathleen; Scovassi, A Ivana; Screaton, Robert A; Screen, Mark; Seca, Hugo; Sedej, Simon; Segatori, Laura; Segev, Nava; Seglen, Per O; Segui-Simarro, Jose M; Segura-Aguilar, Juan; Seki, Ekihiro; Sell, Christian; Selliez, Iban; Semenkovich, Clay F; Semenza, Gregg L; Sen, Utpal; Serra, Andreas L; Serrano-Puebla, Ana; Sesaki, Hiromi; Setoguchi, Takao; Settembre, Carmine; Shacka, John J; Shajahan-Haq, Ayesha N; Shapiro, Irving M; Sharma, Shweta; She, Hua; Shen, C-K James; Shen, Chiung-Chyi; Shen, Han-Ming; Shen, Sanbing; Shen, Weili; Sheng, Rui; Sheng, Xianyong; Sheng, Zu-Hang; Shepherd, Trevor G; Shi, Junyan; Shi, Qiang; Shi, Qinghua; Shi, Yuguang; Shibutani, Shusaku; Shibuya, Kenichi; Shidoji, Yoshihiro; Shieh, Jeng-Jer; Shih, Chwen-Ming; Shimada, Yohta; Shimizu, Shigeomi; Shin, Dong Wook; Shinohara, Mari L; Shintani, Michiko; Shintani, Takahiro; Shioi, Tetsuo; Shirabe, Ken; Shiri-Sverdlov, Ronit; Shirihai, Orian; Shore, Gordon C; Shu, Chih-Wen; Shukla, Deepak; Sibirny, Andriy A; Sica, Valentina; Sigurdson, Christina J; Sigurdsson, Einar M; Sijwali, Puran Singh; Sikorska, Beata; Silveira, Wilian A; Silvente-Poirot, Sandrine; Silverman, Gary A; Simak, Jan; Simmet, Thomas; Simon, Anna Katharina; Simon, Hans-Uwe; Simone, Cristiano; Simons, Matias; Simonsen, Anne; Singh, Rajat; Singh, Shivendra V; Singh, Shrawan K; Sinha, Debasish; Sinha, Sangita; Sinicrope, Frank A; Sirko, Agnieszka; Sirohi, Kapil; Sishi, Balindiwe Jn; Sittler, Annie; Siu, Parco M; Sivridis, Efthimios; Skwarska, Anna; Slack, Ruth; Slaninova, Iva; Slavov, Nikolai; Smaili, Soraya S; Smalley, Keiran Sm; Smith, Duncan R; Soenen, Stefaan J; Soleimanpour, Scott A; Solhaug, Anita; Somasundaram, Kumaravel; Son, Jin H; Sonawane, Avinash; Song, Chunjuan; Song, Fuyong; Song, Hyun Kyu; Song, Ju-Xian; Song, Wei; Soo, Kai Y; Sood, Anil K; Soong, Tuck Wah; Soontornniyomkij, Virawudh; Sorice, Maurizio; Sotgia, Federica; Soto-Pantoja, David R; Sotthibundhu, Areechun; Sousa, Maria Joao; Spaink, Herman P; Span, Paul N; Spang, Anne; Sparks, Janet D; Speck, Peter G; Spector, Stephen A; Spies, Claudia D; Springer, Wolfdieter; Clair, Daret St; Stacchiotti, Alessandra; Staels, Bart; Stang, Michael T; Starczynowski, Daniel T; Starokadomskyy, Petro; Steegborn, Clemens; Steele, John W; Stefanis, Leonidas; Steffan, Joan; Stellrecht, Christine M; Stenmark, Harald; Stepkowski, Tomasz M; Stern, Stephan T; Stevens, Craig; Stockwell, Brent R; Stoka, Veronika; 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Vasko, Radovan; Vavvas, Demetrios G; Vega-Naredo, Ignacio; Velasco, Guillermo; Velentzas, Athanassios D; Velentzas, Panagiotis D; Vellai, Tibor; Vellenga, Edo; Vendelbo, Mikkel Holm; Venkatachalam, Kartik; Ventura, Natascia; Ventura, Salvador; Veras, Patricia St; Verdier, Mireille; Vertessy, Beata G; Viale, Andrea; Vidal, Michel; Vieira, Helena LA; Vierstra, Richard D; Vigneswaran, Nadarajah; Vij, Neeraj; Vila, Miquel; Villar, Margarita; Villar, Victor H; Villarroya, Joan; Vindis, Cecile; Viola, Giampietro; Viscomi, Maria Teresa; Vitale, Giovanni; Vogl, Dan T; Voitsekhovskaja, Olga V; von Haefen, Clarissa; von Schwarzenberg, Karin; Voth, Daniel E; Vouret-Craviari, Valerie; Vuori, Kristina; Vyas, Jatin M; Waeber, Christian; Walker, Cheryl Lyn; Walker, Mark J; Walter, Jochen; Wan, Lei; Wan, Xiangbo; Wang, Bo; Wang, Caihong; Wang, Chao-Yung; Wang, Chengshu; Wang, Chenran; Wang, Chuangui; Wang, Dong; Wang, Fen; Wang, Fuxin; Wang, Guanghui; Wang, Hai-Jie; Wang, Haichao; Wang, Hong-Gang; Wang, Hongmin; Wang, Horng-Dar; Wang, Jing; Wang, Junjun; Wang, Mei; Wang, Mei-Qing; Wang, Pei-Yu; Wang, Peng; Wang, Richard C; Wang, Shuo; Wang, Ting-Fang; Wang, Xian; Wang, Xiao-Jia; Wang, Xiao-Wei; Wang, Xin; Wang, Xuejun; Wang, Yan; Wang, Yanming; Wang, Ying; Wang, Ying-Jan; Wang, Yipeng; Wang, Yu; Wang, Yu Tian; Wang, Yuqing; Wang, Zhi-Nong; Wappner, Pablo; Ward, Carl; Ward, Diane McVey; Warnes, Gary; Watada, Hirotaka; Watanabe, Yoshihisa; Watase, Kei; Weaver, Timothy E; Weekes, Colin D; Wei, Jiwu; Weide, Thomas; Weihl, Conrad C; Weindl, Gunther; Weis, Simone Nardin; Wen, Longping; Wen, Xin; Wen, Yunfei; Westermann, Benedikt; Weyand, Cornelia M; White, Anthony R; White, Eileen; Whitton, J Lindsay; Whitworth, Alexander J; Wiels, Joelle; Wild, Franziska; Wildenberg, Manon E; Wileman, Tom; Wilkinson, Deepti Srinivas; Wilkinson, Simon; Willbold, Dieter; Williams, Chris; Williams, Katherine; Williamson, Peter R; Winklhofer, Konstanze F; Witkin, Steven S; Wohlgemuth, Stephanie E; Wollert, Thomas; Wolvetang, Ernst J; Wong, Esther; Wong, G William; Wong, Richard W; Wong, Vincent Kam Wai; Woodcock, Elizabeth A; Wright, Karen L; Wu, Chunlai; Wu, Defeng; Wu, Gen Sheng; Wu, Jian; Wu, Junfang; Wu, Mian; Wu, Min; Wu, Shengzhou; Wu, William Kk; Wu, Yaohua; Wu, Zhenlong; Xavier, Cristina Pr; Xavier, Ramnik J; Xia, Gui-Xian; Xia, Tian; Xia, Weiliang; Xia, Yong; Xiao, Hengyi; Xiao, Jian; Xiao, Shi; Xiao, Wuhan; Xie, Chuan-Ming; Xie, Zhiping; Xie, Zhonglin; Xilouri, Maria; Xiong, Yuyan; Xu, Chuanshan; Xu, Congfeng; Xu, Feng; Xu, Haoxing; Xu, Hongwei; Xu, Jian; Xu, Jianzhen; Xu, Jinxian; Xu, Liang; Xu, Xiaolei; Xu, Yangqing; Xu, Ye; Xu, Zhi-Xiang; Xu, Ziheng; Xue, Yu; Yamada, Takahiro; Yamamoto, Ai; Yamanaka, Koji; Yamashina, Shunhei; Yamashiro, Shigeko; Yan, Bing; Yan, Bo; Yan, Xianghua; Yan, Zhen; Yanagi, Yasuo; Yang, Dun-Sheng; Yang, Jin-Ming; Yang, Liu; Yang, Minghua; Yang, Pei-Ming; Yang, Peixin; Yang, Qian; Yang, Wannian; Yang, Wei Yuan; Yang, Xuesong; Yang, Yi; Yang, Ying; Yang, Zhifen; Yang, Zhihong; Yao, Meng-Chao; Yao, Pamela J; Yao, Xiaofeng; Yao, Zhenyu; Yao, Zhiyuan; Yasui, Linda S; Ye, Mingxiang; Yedvobnick, Barry; Yeganeh, Behzad; Yeh, Elizabeth S; Yeyati, Patricia L; Yi, Fan; Yi, Long; Yin, Xiao-Ming; Yip, Calvin K; Yoo, Yeong-Min; Yoo, Young Hyun; Yoon, Seung-Yong; Yoshida, Ken-Ichi; Yoshimori, Tamotsu; Young, Ken H; Yu, Huixin; Yu, Jane J; Yu, Jin-Tai; Yu, Jun; Yu, Li; Yu, W Haung; Yu, Xiao-Fang; Yu, Zhengping; Yuan, Junying; Yuan, Zhi-Min; Yue, Beatrice Yjt; Yue, Jianbo; Yue, Zhenyu; Zacks, David N; Zacksenhaus, Eldad; Zaffaroni, Nadia; Zaglia, Tania; Zakeri, Zahra; Zecchini, Vincent; Zeng, Jinsheng; Zeng, Min; Zeng, Qi; Zervos, Antonis S; Zhang, Donna D; Zhang, Fan; Zhang, Guo; Zhang, Guo-Chang; Zhang, Hao; Zhang, Hong; Zhang, Hong; Zhang, Hongbing; Zhang, Jian; Zhang, Jian; Zhang, Jiangwei; Zhang, Jianhua; Zhang, Jing-Pu; Zhang, Li; Zhang, Lin; Zhang, Lin; Zhang, Long; Zhang, Ming-Yong; Zhang, Xiangnan; Zhang, Xu Dong; Zhang, Yan; Zhang, Yang; Zhang, Yanjin; Zhang, Yingmei; Zhang, Yunjiao; Zhao, Mei; Zhao, Wei-Li; Zhao, Xiaonan; Zhao, Yan G; Zhao, Ying; Zhao, Yongchao; Zhao, Yu-Xia; Zhao, Zhendong; Zhao, Zhizhuang J; Zheng, Dexian; Zheng, Xi-Long; Zheng, Xiaoxiang; Zhivotovsky, Boris; Zhong, Qing; Zhou, Guang-Zhou; Zhou, Guofei; Zhou, Huiping; Zhou, Shu-Feng; Zhou, Xu-Jie; Zhu, Hongxin; Zhu, Hua; Zhu, Wei-Guo; Zhu, Wenhua; Zhu, Xiao-Feng; Zhu, Yuhua; Zhuang, Shi-Mei; Zhuang, Xiaohong; Ziparo, Elio; Zois, Christos E; Zoladek, Teresa; Zong, Wei-Xing; Zorzano, Antonio; Zughaier, Susu M

PMCID:4835977

PMID: 26799652

ISSN: 1554-8635

CID: 1922322

Frontiers in endocrinology. 2016:7.DOI: 10.3389/fendo.2016.00062

Sex and Immunogen-Specific Benefits of Immunotherapy Targeting Islet Amyloid Polypeptide in Transgenic and Wild-Type Mice

Krishnamurthy, Pavan K; Rajamohamedsait, Hameetha B; Gonzalez, Veronica; Rajamohamedsait, Wajitha J; Ahmed, Nawal; Krishnaswamy, Senthilkumar; Sigurdsson, Einar M

Type 2 diabetes mellitus is characterized by the deposition of islet amyloid polypeptide (IAPP) as amyloid in islets, a process thought to be toxic to beta-cells. To determine the feasibility of targeting these aggregates therapeutically, we vaccinated transgenic (Tg) mice that overexpress human IAPP and were fed a high-fat diet to promote their diabetic phenotype. Our findings indicate that prophylactic vaccination with IAPP and its derivative IAPP7-19-TT, protects wild-type female mice, but not males, from obesity-induced early mortality, and the derivative showed a strong trend for prolonging the lifespan of Tg females but not males. Furthermore, IAPP7-19-TT-immunized Tg females cleared a glucose bolus more efficiently than controls, while IAPP-immunized Tg females showed an impaired ability to clear a glucose bolus compared to their adjuvant injected Tg controls. Interestingly, IAPP or IAPP7-19-TT treatments had no effect on glucose clearance in Tg males. Overall, these beneficial effects of IAPP targeted immunization depend on Tg status, sex, and immunogen. Hence, future studies in this field should carefully consider these variables that clearly affect the therapeutic outcome. In conclusion, IAPP targeting immunotherapy may have benefits in patients with type 2 diabetes.

PMCID:4907063

PMID: 27379014

ISSN: 1664-2392

CID: 2175782

Trends in molecular medicine. 2015:21(6):394-402.DOI: 10.1016/j.molmed.2015.03.003

Tau immunotherapy for Alzheimer's disease

Pedersen, Jan Torleif; Sigurdsson, Einar M

Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-beta (Abeta) plaques, their clearance may be clinically more efficacious than removing Abeta when cognitive deficits become evident in AD. Several complementary mechanisms of antibody-mediated removal of tau aggregates are likely to act in concert and the importance of each one may depend on antibody properties, the disease, and its stage. Clinical trials of tau immunotherapy are already underway and several more are likely to be initiated in the near future.

PMID: 25846560

ISSN: 1471-499x

CID: 1644542

Journal of biological chemistry. 2015:290(16):10229-41.DOI: 10.1074/jbc.M115.641738

Specific Amyloid beta Clearance by a Catalytic Antibody Construct

Planque, Stephanie A; Nishiyama, Yasuhiro; Sonoda, Sari; Lin, Yan; Taguchi, Hiroaki; Hara, Mariko; Kolodziej, Steven; Mitsuda, Yukie; Gonzalez, Veronica; Sait, Hameetha B R; Fukuchi, Ken-Ichiro; Massey, Richard J; Friedland, Robert P; O'Nuallain, Brian; Sigurdsson, Einar M; Paul, Sudhir

Classical immunization methods do not generate catalytic antibodies (catabodies), but recent findings suggest that the innate antibody repertoire is a rich catabody source. We describe the specificity and amyloid beta (Abeta)-clearing effect of a catabody construct engineered from innate immunity principles. The catabody recognized the Abeta C terminus noncovalently and hydrolyzed Abeta rapidly, with no reactivity to the Abeta precursor protein, transthyretin amyloid aggregates, or irrelevant proteins containing the catabody-sensitive Abeta dipeptide unit. The catabody dissolved preformed Abeta aggregates and inhibited Abeta aggregation more potently than an Abeta-binding IgG. Intravenous catabody treatment reduced brain Abeta deposits in a mouse Alzheimer disease model without inducing microgliosis or microhemorrhages. Specific Abeta hydrolysis appears to be an innate immune function that could be applied for therapeutic Abeta removal.

PMCID:4400338

PMID: 25724648

ISSN: 1083-351x

CID: 1544012

Journal of neuroscience. 2014:34(50):16835-50.DOI: 10.1523/JNEUROSCI.2755-14.2014

Antibody-derived in vivo imaging of tau pathology

Krishnaswamy, Senthilkumar; Lin, Yan; Rajamohamedsait, Wajitha J; Rajamohamedsait, Hameetha B; Krishnamurthy, Pavan; Sigurdsson, Einar M

Antibodies or their derivatives as imaging probes for pathological tau protein have great potential, but have not been well studied. In particular, smaller, single-chain-variable antibody fragments (scFv's) are attractive for detecting tau lesions in live subjects. Here, we generated libraries of scFv's and identified numerous phospho-tau-selective scFv's. Peripheral injection of one of these scFv's consistently resulted in a strong in vivo brain signal in transgenic tauopathy mice, but not in wild-type or amyloid-beta plaque mice. The parent tau antibody provided similar results, albeit with a weaker signal intensity. The imaging signal correlated very well with colocalization of the probe with intraneuronal tau aggregates. Both were associated with markers of endosomes, autophagosomes, and lysosomes, suggesting their interaction in these degradation pathways. Such specific antibody-derived imaging probes have great potential as diagnostic markers for Alzheimer's disease and related tauopathies.

PMCID:4261104

PMID: 25505335

ISSN: 0270-6474

CID: 1424802

Neuro-degenerative diseases. 2014:13(2-3):103-6.DOI: 10.1159/000354491

Tau Immunotherapy and Imaging

Sigurdsson, Einar M

Disappointing findings from recent phase III trials on amyloid-beta (Abeta) immunotherapy for Alzheimer's disease (AD) have shifted the focus of such treatments to the tau protein. As tau pathology correlates better with the degree of dementia than Abeta plaque burden, it is a more attractive target once cognitive impairments are evident, while Abeta therapies may be better suited for the presymptomatic phase of the disease. Over 12 years ago, we initiated a tau immunotherapy program, seeking to alleviate the functional impairments associated with tau lesions in tauopathies. We have reported that various active and passive tau immunizations diminish tau pathology and improve function, including cognition, in different mouse models. Both extra- and intracellular pathways are likely involved. The antibodies may block the spread of tau pathology via microglial phagocytosis of the antibody-tau complex and facilitate lysosomal tau clearance in neurons after endosomal uptake. We have observed such antibody internalization following intracarotid injection in mice and in various culture models. These include brain slices and primary neurons from tangle mice as well as human neuroblastoma cell lines. Antibody targeting of different intracellular protein aggregates, including alpha-synuclein, Abeta and superoxide dismutase has been reported by others. Now, several laboratories have confirmed and extended our findings using various active and passive tau immunizations in different models, thereby clearly establishing the feasibility of this approach for clinical trials. We are also working on imaging approaches to monitor tau pathology, its consequences and the efficacy of treatments. Dire need exists for such diagnostic methods for tauopathies. Overall, therapies and diagnostic tools targeting tau pathology have a great potential for AD and other tauopathies. (c) 2013 S. Karger AG, Basel.

PMCID:3946316

PMID: 24029727

ISSN: 1660-2854

CID: 712672