Searched for: person:hernar04
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FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease
Yan, Tingxiang; Liang, Jingjing; Gao, Ju; Wang, Luwen; Fujioka, Hisashi; Zhu, Xiaofeng; Wang, Xinglong; Weiner, Michael W; Schuff, Norbert; Rosen, Howard J; Miller, Bruce L; Perry, David; Aisen, Paul; Toga, Arthur W; Jimenez, Gustavo; Donohue, Michael; Gessert, Devon; Harless, Kelly; Salazar, Jennifer; Cabrera, Yuliana; Walter, Sarah; Hergesheimer, Lindsey; Toga, Arthur W; Crawford, Karen; Neu, Scott; Schneider, Lon S; Pawluczyk, Sonia; Becerra, Mauricio; Teodoro, Liberty; Spann, Bryan M; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S; Albers, Colleen S; Knopman, David; Johnson, Kris; Graff-Radford, Neill R; Parfitt, Francine; Poki-Walker, Kim; Jagust, William; Landau, Susan; Trojanowki, John Q; Shaw, Leslie M; Karlawish, Jason H; Wolk, David A; Vaishnavi, Sanjeev; Clark, Christopher M; Arnold, Steven E; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Beckett, Laurel; Harvey, Danielle; DeCArli, Charles; Fletcher, Evan; Maillard, Pauline; Olichney, John; Carmichael, Owen; Green, Robert C; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad A; Saykin, Andrew J; Foroud, Tatiana M; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Brosch, Jared R; Herring, Scott; Morris, John; Raichle, Marc; Holtzman, David; Morris, John C; Cairns, Nigel J; Franklin, Erin; Taylor-Reinwald, Lisa; Ances, Beau; Winkfield, David; Carroll, Maria; Oliver, Angela; Creech, Mary L; Mintun, Mark A; Schneider, Stacy; Kuller, Lew; Mathis, Chet; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Paul, Steven; Relkin, Norman; Chiang, Gloria; Lin, Michael; Ravdin, Lisa; Davies, Peter; Mesulam, M Marcel; Mesulam, Marek-Marsel; Rogalski, Emily; Lipowski, Kristine; Weintraub, Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Snyder, Peter J; Montine, Tom; Donohue, Michael; Thal, Lean; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Thompson, Paul; Woo, Ellen; Silverman, Daniel H S; Teng, Edmond; Kremen, Sarah; Apostolova, Liana; Tingus, Kathleen; Lu, Po H; Bartzokis, George; Koeppe, Robert A; Ziolkowski, Jaimie; Heidebrink, Judith L; Lord, Joanne L; Foster, Norm; Albert, Marilyn; Onyike, Chiadi; D'Agostino, Daniel; Kielb, Stephanie; Quinn, Joseph; Silbert, Lisa C; Lind, Betty; Kaye, Jeffrey A; Carter, Raina; Dolen, Sara; Villanueva-Meyer, Javier; Pavlik, Valory; Pacini, Nathaniel; Lamb, Ashley; Kass, Joseph S; Doody, Rachelle S; Shibley, Victoria; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Yeh, Randy; Marson, Daniel; Geldmacher, David; Natelson, Marissa; Griffith, Randall; Clark, David; Brockington, John; Grossman, Hillel; Mitsis, Effie; Shah, Raj C; Lamar, Melissa; Samuels, Patricia; Sadowski, Martin; Sheikh, Mohammed O; Singleton-Garvin, Jamika; Ulysse, Anaztasia; Gaikwad, Mrunalini; Doraiswamy, P Murali; James, Olga; Borges-Neto, Salvador; Wong, Terence Z; Coleman, Edward; Smith, Charles D; Jicha, Greg; Hardy, Peter; El Khouli, Riham; Oates, Elizabeth; Conrad, Gary; Porsteinsson, Anton P; Martin, Kim; Kowalksi, Nancy; Keltz, Melanie; Goldstein, Bonnie S; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Thai, Gaby; Pierce, Aimee; Yanez, Beatriz; Sosa, Elizabeth; Witbracht, Megan; Potkin, Steven; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Swerdlow, Russell H; Brooks, William M; van Dyck, Christopher H; Carson, Richard E; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Oyonumo, Ntekim E; Allard, Joanne; Ogunlana, Olu; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M; Yesavage, Jerome; Taylor, Joy L; Chao, Steven; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Scharre, Douglas W; Kataki, Maria; Tarawneh, Rawan; Zimmerman, Earl A; Celmins, Dzintra; Hart, David; Flashman, Laura A; Seltzer, Marc; Hynes, Mary L; Santulli, Robert B; Sink, Kaycee M; Yang, Mia; Mintz, Akiva; Miller, Delwyn D; Smith, Karen Ekstam; Koleva, Hristina; Nam, Ki Won; Shim, Hyungsub; Schultz, Susan K; Smith, Amanda; Leach, Christi; Raj, Balebail Ashok; Fargher, Kristin; Reiman, Eric M; Chen, Kewei; Tariot, Pierre; Burke, Anna; Hetelle, Joel; DeMarco, Kathryn; Trncic, Nadira; Fleisher, Adam; Reeder, Stephanie; Zamrini, Edward; Belden, Christine M; Sirrel, Sherye A; Duara, Ranjan; Greig-Custo, Maria T; Rodriguez, Rosemarie; Bernick, Charles; Munic, Donna; Khachaturian, Zaven; Buckholtz, Neil; Hsiao, John; Potter, William; Fillit, Howard; Hefti, Franz; Sadowsky, Carl; Villena, Teresa; Hsiung, Ging-Yuek Robin; Mudge, Benita; Sossi, Vesna; Feldman, Howard; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Pavlosky, William; Rachinsky, Irina; Drost, Dick; Kertesz, Andrew; Black, Sandra; Stefanovic, Bojana; Heyn, Chrinthaka; Ott, Brian R; Tremont, Geoffrey; Daniello, Lori A; Bodge, Courtney; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Lee, Athena; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabeth; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick; Finger, Elizabeth; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Frank, Richard; Fox, Nick; Logovinsky, Veronika; Corrillo, Maria; Sorensen, Greg
Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.
PMCID:6972869
PMID: 31964863
ISSN: 2041-1723
CID: 5134432
Multimodal Hippocampal Subfield Grading For Alzheimer's Disease Classification
Hett, Kilian; Vinh-Thong Ta; Catheline, Gwenaelle; Tourdias, Thomas; Manjon, Jose V.; Coupe, Pierrick; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Mesulam, M. Marcel; Potter, William; Snyder, Peter; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Decarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Lean; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Love, Marissa Natelson; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Grossman, Hillel; Mitsis, Effie; Shah, Raj C.; deToledo-Morrell, Leyla; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Albert, Marilyn; Onyike, Chiadi; D\Agostino, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Borges-Neto, Salvador; Wong, Terence Z.; Coleman, Edward; Levey, Allan I.; Lah, James J.; Cella, Janet S.; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Graff-Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Rachisky, Irina; Trost, Dick; Kertesz, Andrew; Bernick, Charles; Munic, Donna; Lipowski, Kristine; Weintraub, M. A. Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Fletcher, Evan; Maillard, Pauline; Olichney, John; Carmichael, Owen; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Burke, Anna; Trncic, Nadira; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Ponto, Laura L. Boles; Shim, Hyungsub; Smith, Karen Ekstam; Relkin, Norman; Chaing, Gloria; Lin, Michael; Ravdin, Lisa; Smith, Amanda; Raj, Balebail Ashok; Fargher, Kristin
ISI:000487586600036
ISSN: 2045-2322
CID: 4155602
18F-florbetapir Positron Emission Tomography-determined Cerebral beta-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery
Klinger, Rebecca Y; James, Olga G; Borges-Neto, Salvador; Bisanar, Tiffany; Li, Yi-Ju; Qi, Wenjing; Berger, Miles; Terrando, Niccola; Newman, Mark F; Doraiswamy, P Murali; Mathew, Joseph P; Weiner, Michael W; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J;Shaw, Leslie M; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, David; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B; Mason, Jennifer; Sim, Iris; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCArli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A; Foster, Norm; Reiman, Eric M; Chen, Kewei; Mathis, Chet; Landau, Susan; Morris, John C; Cairns, Louis Nigel J; Franklin, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Lean; Thal, Leon; Buckholtz, Neil; Snyder, Peter J; Albert, Marilyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S; Pawluczyk, Sonia; Becerra, Mauricio; Teodoro, Liberty; Spann, Bryan M; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L; Lord, Joanne L; Mason, Sara S; Albers, Colleen S; Knopman, David; Johnson, Kris; Doody, Rachelle S; Villanueva-Meyer, Javier; Pavlik, Valory; Shibley, Victoria; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Ances, Beau; Carroll, Maria; Creech, Mary L; Mintun, Mark A; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Geldmacher, David; Love, Marissa Natelson; Griffith, Randall; Clark, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; Shah, Raj C; deToledo-Morrell, Leyla; Duara, Ranjan; Greig-Custo, Maria T; Barker, Warren; Onyike, Chiadi; D'Agostino, Daniel; Kielb, Stephanie; Sadowski, Martin; Sheikh, Mohammed O; Ulysse, Anaztasia; Gaikwad, Mrunalini; Petrella, Jeffrey R; Wong, Terence Z; Coleman, Edward; Arnold, Steven E; Karlawish, Jason H; Wolk, David A; Clark, Christopher M; Smith, Charles D; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Porsteinsson, Anton P; Goldstein, Bonnie S; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Potkin, Steven G; Preda, Adrian; Nguyen, Dana; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Swerdlow, Russell H; Brooks, William M; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H S; Lu, Po H; Bartzokis, George; Graff-Radford, Neill R; Parfitt, Francine; Poki-Walker, Kim; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Brosch, Jared R; Herring, Scott; van Dyck, Christopher H; Carson, Richard E; MacAvoy, Martha G; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Robin; Mudge, Benita; Sossi, Vesna; Feldman, Howard; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Trost, Dick; Kertesz, Andrew; Bernick, Charles; Munic, Donna; Mesulam, Marek-Marsel; Rogalski, Emily; Lipowski, Kristine; Weintraub, Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad; Yesavage, Jerome; Taylor, Joy L; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N; Belden, Christine M; Jacobson, Sandra A; Sirrel, Sherye A; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Fletcher, Evan; Maillard, Pauline; Olichney, John; DeCarli, Charles; Carmichael, Owen; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Dr Rob; Asthana, Sanjay; Carlsson, Cynthia M; Tariot, Pierre; Burke, Anna; Milliken, Ann Marie; Trncic, Nadira; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W; Kataki, Maria; Kelley, Brendan; Zimmerman, Earl A; Celmins, Dzintra; Brown, Alice D; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Flashman, Laura A; Seltzer, Marc; Hynes, Mary L; Santulli, Robert B; Sink, Kaycee M; Gordineer, Leslie; Williamson, Jeff D; Garg, Pradeep; Watkins, Franklin; Ott, Brian R; Tremont, Geoffrey; Daiello, Lori A; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J; Miller, Bruce L; Perry, David; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Rachinsky, Irina; Rogers, John; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K; Smith, Karen Ekstam; Koleva, Hristina; Nam, Ki Won; Shim, Hyungsub; Relkin, Norman; Chiang, Gloria; Lin, Michael; Ravdin, Lisa; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Neylan, Thomas; Grafman, Jordan; Thomas, Ronald G; Davis, Melissa; Morrison, Rosemary; Hayes, Jacqueline; Finely, Shannon; Cairns, Nigel J; Householder, Erin; Crawford, Karen; Friedl, Karl; Fleischman, Debra; Arfanakis, Konstantinos; Varon, Daniel; Greig, Maria T; Martin, Kimberly S; Preda, Adrian; Massoglia, Dino; Brawman-Mintzer, Olga; Martinez, Walter; Behan, Kelly; Johnson, Sterling C; Fruehling, J Jay; Harding, Sandra; Peskind, Elaine R; Petrie, Eric C; Li, Gail; Furst, Ansgar J; Chao, Steven; Blumenthal, James A; Karhausen, Jorn A; Kertai, Miklos D; Podgoreanu, Mihai V; Stafford-Smith, Mark; Swaminathan, Madhav; Warner, David S; Funk, Bonita L; Balajonda, Narai; Brassard, Rachele; Cooter, Mary; Toulgoat-Dubois, Yanne; Waweru, Peter; Babyak, Michael A; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A; Sketch, Michael H; Bennett, Ellen R; Graffagnino, Carmelo; Laskowitz, Daniel T; Strittmatter, Warren J; Collins, Kevin; Smigla, Greg; Shearer, Ian; D'Amico, Thomas A; Daneshmand, Mani A; Gaca, R Jeffrey G; Glower, Donald D; Haney, Jack; Harpole, R David; Hartwig, Mathew G; Hughes, G Chad; Klapper, Jacob A; Lin, Shu S; Lodge, Andrew J; Milano, Carmelo A; Plichta, Ryan P; Schroeder, Jacob N; Smith, Peter K; Tong, Betty C
BACKGROUND:Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS:Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype. RESULTS:The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls. CONCLUSIONS:In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.
PMCID:5849499
PMID: 29389750
ISSN: 1528-1175
CID: 2994312
Selective and state-dependent changes in CSF abeta42 levels in cognitively-intact elderly with late life major depression [Meeting Abstract]
Pomara, N; Nierenberg, J; Bruno, D; Reichert, C; Osorio, R; Sarreal, A; Hernando, R; Marmar, C; Wisniewski, T; Zetterberg, H; Blennow, K
Background: Numerous studies have linked depressive symptoms, or syndromal depression, to increased risk for Alzheimer's disease (AD) irrespective of its onset age. The neurobiological basis for this association, however, remains poorly understood. Studies which have examined biomarkers of AD in peripheral and central tissues in depression, including CSF Abeta42 (Abeta42) and brain amyloid using PET ligands, have provided conflicting results. These discrepant results may have been due to methodological differences across studies, including heterogeneity in study populations (e.g., inclusion of individuals with mild cognitive impairment) and the use of approaches for detecting depression (e.g., patients' self-ratings) that lack diagnostic specificity. In addition, only a few studies have employed structured interviews based on DSM diagnostic criteria or standardized pre-analytical and laboratory procedures for quantifying Abeta. Finally, all of the existing studies have been limited to cross sectional comparisons based on a single Abeta determination; thus, it is not known if these abnormalities persist over time and if depressive symptoms influence Abeta levels. The current study was conducted to address the aforementioned limitations. Methods: Our baseline sample consisted of 47 subjects aged 60 years and older; 28 with LMDD and 19 controls. Of the 47 older subjects, 31 were e4 non-carriers and 16 were e4 carriers. All subjects were cognitively-intact and had a) no evidence of dementia, b) a Mini-Mental State Exam score of at least 28, and c) no gross MRI abnormalities other than white matter hyperintensities. CSF collection was repeated after 3 years for 36 of these individuals: 19 with LLMD and 17 controls. We evaluated the effects of diagnosis and time on Abeta42 levels with 2 x 2 repeated measures ANOVA. Results: Longitudinal comparisons of controls and LLMD revealed that the LLMD group was significantly less depressed at follow up than at baseline, as determined by the HAM-D, whereas controls remained unchanged. There was a significant interaction between diagnosis and time on CSF Abeta42 levels. Importantly, the reductions in depressive symptoms observed over time were significantly correlated with increases in CSF Abeta42 levels, both in the entire cohort (r =-.451, p =.006) and within the LLMD group (r =-.547, p =.015), but not in the control group (p =.809). The same relationship was not significant with Abeta40 (Pomara et al., 2016). Performance on cognitive indices remained unchanged and was not significantly correlated with changes in AD Biomarkers. Conclusions: Cognitively-intact, elderly individuals with LLMD, who were more depressed at baseline, but less depressed at the 3 year follow-up, showed both a reduction in baseline CSF Abeta42 (Pomara et al., 2012) and elevation in Abeta42 at 3 year follow-up. In addition, changes in CSF Abeta42 were correlated with changes in depressive symptoms. Future studies should determine if these state-dependent changes in Abeta42 mediate the increased risk of AD contributed by LLMD. If this is the case, the need for more aggressive treatment of LLMD cannot be underestimated
EMBASE:613896606
ISSN: 1740-634x
CID: 2397672
State-dependent alterations in cerebrospinal fluid Abeta42 levels in cognitively intact elderly with late-life major depression
Pomara, Nunzio; Bruno, Davide; Osorio, Ricardo S; Reichert, Chelsea; Nierenberg, Jay; Sarreal, Antero S; Hernando, Raymundo T; Marmar, Charles R; Wisniewski, Thomas; Zetterberg, Henrik; Blennow, Kaj
Depression has been linked to Alzheimer's disease as either an increased risk factor for its development or as a prodromal symptom. The neurobiological basis for such an association, however, remains poorly understood. Numerous studies have examined whether changes in amyloid beta (Abeta) metabolism, which are implicated in the pathogenesis of Alzheimer's disease, are also found in depression. In this paper, we investigated the relationship between depressive symptoms and cerebrospinal fluid (CSF) Abeta indices in otherwise healthy, cognitively normal elderly with late-life major depression (LLMD) and controls using a longitudinal approach, which is a novel contribution toward the literature. Significantly lower levels of CSF Abeta42 were observed in the LLMD group at baseline and were associated with more severe depressive symptoms. During longitudinal follow-up, the depressed group remained cognitively unchanged, but was significantly less depressed than at baseline. A greater improvement in depressive symptoms was associated with increases in CSF Abeta42 levels in both groups. Increases in CSF Abeta42 and Abeta40 were also associated with increased CSF total-tau levels. Our results suggest that LLMD may be associated with state-dependent effects of CSF Abeta42 levels. Future studies should determine whether the association reflects state-dependent changes in neuronal activity and/or brain amyloid burden in depression.
PMCID:5007146
PMID: 27508979
ISSN: 1473-558x
CID: 2213652
Lower CSF amyloid beta peptides and higher F2-isoprostanes in cognitively intact elderly individuals with major depressive disorder
Pomara, Nunzio; Bruno, Davide; Sarreal, Antero S; Hernando, Raymundo T; Nierenberg, Jay; Petkova, Eva; Sidtis, John J; Wisniewski, Thomas M; Mehta, Pankaj D; Pratico, Domenico; Zetterberg, Henrik; Blennow, Kaj
OBJECTIVE: Major depressive disorder is common in the elderly, and symptoms are often not responsive to conventional antidepressant treatment, especially in the long term. Soluble oligomeric and aggregated forms of amyloid beta peptides, especially amyloid beta 42, impair neuronal and synaptic function. Amyloid beta 42 is the main component of plaques and is implicated in Alzheimer's disease. Amyloid beta peptides also induce a depressive state in rodents and disrupt major neurotransmitter systems linked to depression. The authors assessed whether major depression was associated with CSF levels of amyloid beta, tau protein, and F2-isoprostanes in elderly individuals with major depressive disorder and age-matched nondepressed comparison subjects. METHOD: CSF was obtained from 47 cognitively intact volunteers (major depression group, N=28; comparison group, N=19) and analyzed for levels of soluble amyloid beta, total and phosphorylated tau proteins, and isoprostanes. RESULTS: Amyloid beta 42 levels were significantly lower in the major depression group relative to the comparison group, and amyloid beta 40 levels were lower but only approaching statistical significance. In contrast, isoprostane levels were higher in the major depression group. No differences were observed in total and phosphorylated tau proteins across conditions. Antidepressant use was not associated with differences in amyloid beta 42 levels. CONCLUSIONS: Reduction in CSF levels of amyloid beta 42 may be related to increased brain amyloid beta plaques or decreased soluble amyloid beta production in elderly individuals with major depression relative to nondepressed comparison subjects. These results may have implications for our understanding of the pathophysiology of major depression and for the development of treatment strategies.
PMCID:3586557
PMID: 22764362
ISSN: 0002-953x
CID: 174136
Plasma BDNF levels vary in relation to body weight in females
Pillai, Anilkumar; Bruno, Davide; Sarreal, Antero S; Hernando, Raymundo T; Saint-Louis, Leslie A; Nierenberg, Jay; Ginsberg, Stephen D; Pomara, Nunzio; Mehta, Pankaj D; Zetterberg, Henrik; Blennow, Kaj; Buckley, Peter F
Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted.
PMCID:3388065
PMID: 22768299
ISSN: 1932-6203
CID: 448872
Increased Mental Slowing Associated With the APOE {varepsilon}4 Allele After Trihexyphenidyl Oral Anticholinergic Challenge in Healthy Elderly
Pomara, Nunzio; Belzer, Ken; Hernando, Raymundo; De La Pena, Corazon; Sidtis, John J
Objectives: The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl-induced subjective effects and objective memory performance. Methods: This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo-controlled, three-way, crossover experimental design. All participants received 1.0 mg or 2.0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader's visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2.5, and 5 hours postdrug administration. Results: A 2.0-mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2.0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear-headedness. Conclusion: The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge
PMID: 18239197
ISSN: 1064-7481
CID: 75708
The effect of mifepristone (RU 486) on plasma cortisol in Alzheimer's disease
Pomara, Nunzio; Hernando, Raymundo T; de la Pena, Corazon B; Sidtis, John J; Cooper, Thomas B; Ferris, Steven
The glucocorticoid receptor (GR) antagonist mifepristone (RU-486) has been reported to increase early morning plasma ACTH/cortisol in diverse non-demented populations. This pilot study examined the cortisol response to RU 486 in patients with Alzheimer's disease (AD), a condition associated with abnormalities in various aspects of the hypothalamic-pituitary-adrenal (HPA) axis. Nine AD subjects were randomized in a placebo-controlled parallel study: 4 in the placebo group and 5 in the RU 486 group. Subjects received oral doses of RU 486 (200 mg) or placebo daily for 6-weeks. Morning plasma cortisol was determined at baseline, at 12 h following the first study drug dose, and weekly thereafter. RU 486 resulted in a significant increase in cortisol levels [F(1,6)=65.32; P<0.001]. The magnitude of this increase grew over the course of the study [F(1,6)=63.17; P<0.001], was not related to cortisol suppression after dexamethasone and appeared greater than that reported in the literature in younger populations in response to the same drug regimen. However, further studies with age-matched controls should be done to determine possible AD related changes in this response
PMID: 16770728
ISSN: 0364-3190
CID: 69567
Screaming and physical aggression in nursing homes [Letter]
Pomara, Nunzio; Volavka, Jan; Czobor, P'al; Hernando, Raymundo; Sidtis, John J
PMID: 15956275
ISSN: 1064-7481
CID: 60839
