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Drug-induced reductions in brain amyloid-β levels may adversely affect cognition and behavior by a disruption of functional connectivity homeostasis
Imbimbo, Bruno P; Pomara, Nunzio
PMID: 31337272
ISSN: 1758-2032
CID: 3987072
The recency ratio is related to CSF Amyloid Beta 1-42 levels in MCI-AD
Bruno, Davide; Gleason, Carey E; Koscik, Rebecca L; Pomara, Nunzio; Zetterberg, Henrik; Blennow, Kaj; Johnson, Sterling C
OBJECTIVE:As anti-amyloid therapeutic interventions shift from enrolling patients with Alzheimer's disease (AD) dementia to individuals with pre-clinical disease, the need for sensitive measures that allow for non-invasive, fast, disseminable and cost-effective identification of preclinical status increases in importance. The recency ratio (Rr) is a memory measure that relies on analysis of serial position performance, which has been found to predict cognitive decline and conversion to early mild cognitive impairment (MCI). The aim of this study was to test Rr's sensitivity to cerebrospinal fluid (CSF) levels of the core AD biomarkers in individuals with MCI-AD and controls. METHODS:Baseline data from 126 (110 controls and 16 MCI-AD) participants from the Wisconsin Alzheimer's Disease Research Center were analysed. Partial correlations adjusting for demographics were carried out between CSF measure of amyloid beta (Aβ40, Aβ42 and the 40/42 ratio) and tau (total and phosphorylated), and memory measures (Rr, delayed recall and total recall) derived from the Rey's Auditory Verbal Learning Test. RESULTS:Results indicated that Rr was the most sensitive memory score to Aβ42 levels in MCI-AD, while no memory score correlated significantly with any biomarker in controls. CONCLUSIONS:This study shows that Rr is a sensitive cognitive index of underlying Amyloid β pathology in MCI-AD.
PMID: 30430632
ISSN: 1099-1166
CID: 3457562
Basal Forebrain Resting Functional Activity Associated with Brain Amyloid-β Burden in ε4 Carriers and Older Women: Possible Implications for Baseline Cognition and Response to Amyloid-β-based Preventive Trials
Pomara, Nunzio; Bruno, Davide
PMID: 30720398
ISSN: 1527-1315
CID: 3632042
CSF butyrylcholinesterase and acetyl-cholinesterase activity and their relationship to pro-inflammatory cytokines in late-life major depression [Meeting Abstract]
Pomara, N.; Bruno, D.; Nierenberg, J.; Reichert, C.; Fu, M.; Zetterberg, H.; Blennow, K.
ISI:000458400500124
ISSN: 0924-977x
CID: 3827672
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
The recency ratio as predictor of early MCI
Bruno, Davide; Koscik, Rebecca L; Woodard, John L; Pomara, Nunzio; Johnson, Sterling C
ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline.
PMID: 29667564
ISSN: 1741-203x
CID: 3056222
Pathological Increases in Neuronal Hyperactivity in Selective Cholinergic and Noradrenergic Pathways May Limit the Efficacy of Amyloid-β-Based Interventions in Mild Cognitive Impairment and Alzheimer's Disease
Pomara, Nunzio; Bruno, Davide
In spite of compelling evidence linking amyloid-β (Aβ) disturbances to the pathophysiology of Alzheimer's disease (AD), Aβ-based treatments have consistently failed to produce any beneficial effects both in mild cognitive impairment (MCI) and AD, even with successful reductions of toxic aggregated and soluble Aβ species. Before abandoning both the hypothesis and approach, there is a need to examine some overlooked factors that may have contributed to the lack of efficacy, such as the potential drug-induced increases in neuronal hyperactivity leading to adverse cognitive effects. In particular, we posit that selective cholinergic and noradrenergic pathways will be especially vulnerable to this adverse effect. If confirmed, this idea could help identify a potentially preventable and treatable obstacle for enhancing the efficacy of therapeutic agents in MCI and AD.
PMID: 30480259
ISSN: 2542-4823
CID: 3500562
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
Reduction in CSF STREM2, a biomarker of microglia activation, in elderly depressives [Meeting Abstract]
Pomara, N; Bruno, D; Nierenberg, J; Zetterberg, H; Blennow, K; Heslegrave, A; Foiani, M
Background: Both intense microglia activation and senescence, which respectively lead to marked and reduced inflammatory responses, have each been implicated in the etiology of depression. However, to date, results from postmortem and PET studies of microglial status have been negative or inconclusive, perhaps reflecting the heterogeneity of microglia dysfunction in this disorder, and the lack of specificity of the neuroimaging ligands for microglia. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane innate immune receptor of the immunoglobulin family; in brain, it is found exclusively on microglia. TREM2 variants have been associated with increased risk for AD and other degenerative disorders. It undergoes proteolytic cleavage generating a soluble form (sTREM2), found in CSF, and emerging data suggest that its levels may reflect microglia activation. These considerations prompted us to determine if elderly cognitively-intact individuals with a DSM-IV diagnosis of late-life major depression (LLMD) differ from healthy controls with respect to CSF sTREM2 and its relationship to depressive symptoms. Additionally, because of the association between depression and increased risk for AD, we also determined its relationship to CSF AD biomarkers. Methods: CSF was obtained from 47 older subjects with intact cognition having an MMSE score of at least 28 and no gross MRI abnormalities other than white matter hyperintensities (28 LLMDs, 19 Healthy controls). CSF sTREM2 was determined using an electrochemiluminescence immunoassay. Severity of depression was determined at the baseline and screening visits using the HAM-D. Results: CSF sTREM2 was significantly (p<.05) reduced in LLMD compared to controls. CSF sTREM2 was significantly (negatively) correlated with baseline HAM-D scores in the entire sample and in the depressed group separately. As previously reported in cognitively-intact populations, CSF sTREM2 was significantly (positively) correlated with CSF Abeta42, Abeta40, tau and p-tau. Antidepressant treatment and APOE-e4 status had no effect on CSF sTREM2. Conclusions: The reduction in CSF sTREM2 level in LLMD and its association with more depressive symptoms suggest that decreased rather than increased microglia activation may contribute to the pathophysiology of this disorder. Future studies should determine how lower CSF sTREM2 levels may relate to activated M1 (pro-inflammatory) or M2 (anti-inflammatory) microglia phenotypes and to inflammatory and AD brain PET biomarkers
EMBASE:619901231
ISSN: 1740-634x
CID: 2955442
Basal forebrain mediated increase in brain CRF is associated with increased cholinergic tone and depression
Gollan, Jackie K; Dong, Hongxin; Bruno, Davide; Nierenberg, Jay; Nobrega, Jose N; Grothe, Michel J; Pollock, Bruce G; Marmar, Charles R; Teipel, Stefan; Csernansky, John G; Pomara, Nunzio
PMID: 28477491
ISSN: 1872-7123
CID: 2548752
