Journal Article

DZNE-2021-00223

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.

Franzmeier, N. ; Suárez-Calvet, M. ; Frontzkowski, L. ; Moore, A. ; Hohman, T. J. ; Morenas-Rodriguez, E. ; Nuscher, B. ; Shaw, L. ; Trojanowski, J. Q. ; Dichgans, M.DZNE* ; Kleinberger, G. ; Haass, C.DZNE* ; Ewers, M. (Last author)DZNE* ; Initiative, A. D. N. (Collaboration Author) ; Weiner, M. ; Aisen, P. ; Novak, G. ; Green, R. C. ; Montine, T. ; Petersen, R. ; Gamst, A. ; Thomas, R. G. ; Donohue, M. ; Walter, S. ; Gessert, D. ; Sather, T. ; Beckett, L. ; Harvey, D. ; Kornak, J. ; Jack, C. R. ; Dale, A. ; Bernstein, M. ; Felmlee, J. ; Fox, N. ; Thompson, P. ; Schuff, N. ; Alexander, G. ; DeCarli, C. ; Jagust, W. ; Bandy, D. ; Koeppe, R. A. ; Foster, N. ; Reiman, E. M. ; Chen, K. ; Mathis, C. ; Morris, J. ; Cairns, N. J. ; Taylor-Reinwald, L. ; Trojanowki, J. Q. ; Shaw, L. ; Lee, V. M. Y. ; Korecka, M. ; Toga, A. W. ; Crawford, K. ; Neu, S. ; Saykin, A. J. ; Foroud, T. M. ; Potkin, S. ; Shen, L. ; Kachaturian, Z. ; Frank, R. ; Snyder, P. J. ; Molchan, S. ; Kaye, J. ; Dolen, S. ; Quinn, J. ; Schneider, L. S. ; Pawluczyk, S. ; Spann, B. M. ; Brewer, J. ; Vanderswag, H. ; Heidebrink, J. L. ; Lord, J. L. ; Johnson, K. ; Doody, R. S. ; Villanueva-Meyer, J. ; Chowdhury, M. ; Stern, Y. ; Honig, L. S. ; Bell, K. L. ; Morris, J. C. ; Mintun, M. A. ; Schneider, S. ; Marson, D. ; Griffith, R. ; Clark, D. ; Grossman, H. ; Mitsis, E. ; Romirowsky, A. ; deToledo-Morrell, L. ; Shah, R. C. ; Duara, R. ; Varon, D. ; Roberts, P. ; Albert, M. ; Onyike, C. ; Kielb, S. ; Rusinek, H. ; de Leon, M. J. ; Glodzik, L. ; Doraiswamy, P. M. ; Petrella, J. R. ; Arnold, S. E. ; Karlawish, J. H. ; Wolk, D. ; Smith, C. D. ; Jicha, G. ; Hardy, P. ; Lopez, O. L. ; Oakley, M. A. ; Simpson, D. M. ; Ismail, M. S. ; Brand, C. ; Mulnard, R. A. ; Thai, G. ; Mc-Adams-Ortiz, C. ; Diaz-Arrastia, R. ; Martin-Cook, K. ; DeVous, M. ; Levey, A. I. ; Lah, J. J. ; Cellar, J. S. ; Burns, J. M. ; Anderson, H. S. ; Swerdlow, R. H. ; Bartzokis, G. ; Silverman, D. H. S. ; Lu, P. H. ; Apostolova, L. ; Graff-Radford, N. R. ; Parfitt, F. ; Johnson, H. ; Farlow, M. ; Herring, S. ; Hake, A. M. ; van Dyck, C. H. ; Carson, R. E. ; MacAvoy, M. G. ; Chertkow, H. ; Bergman, H. ; Hosein, C. ; Black, S. ; Stefanovic, B. ; Caldwell, C. ; Hsiung, G. R. ; Feldman, H. ; Assaly, M. ; Kertesz, A. ; Rogers, J. ; Trost, D. ; Bernick, C. ; Munic, D. ; Wu, C.-K. ; Johnson, N. ; Mesulam, M. ; Sadowsky, C. ; Martinez, W. ; Villena, T. ; Turner, R. S. ; Johnson, K. ; Reynolds, B. ; Sperling, R. A. ; Frey, M. ; Johnson, K. A. ; Rosen, A. ; Tinklenberg, J. ; Ashford, W. ; Sabbagh, M. ; Belden, C. ; Jacobson, S. ; Killiany, R. ; Norbash, A. ; Nair, A. ; Obisesan, T. O. ; Wolday, S. ; Bwayo, S. K. ; Lerner, A. ; Hudson, L. ; Ogrocki, P. ; Fletcher, E. ; Carmichael, O. ; Kittur, S. ; Borrie, M. ; Lee, T.-Y. ; Bartha, R. ; Johnson, S. ; Asthana, S. ; Carlsson, C. M. ; Potkin, S. G. ; Preda, A. ; Nguyen, D. ; Tariot, P. ; Fleisher, A. ; Reeder, S. ; Bates, V. ; Capote, H. ; Rainka, M. ; Hendin, B. A. ; Scharre, D. W. ; Kataki, M. ; Zimmerman, E. A. ; Celmins, D. ; Brown, A. D. ; Hosp, H. ; Pearlson, G. D. ; Blank, K. ; Anderson, K. ; Santulli, R. B. ; Schwartz, E. S. ; Williamson, J. D. ; Sink, K. M. ; Watkins, F. ; Ott, B. R. ; Querfurth, H. ; Tremont, G. ; Salloway, S. ; Malloy, P. ; Correia, S. ; Rosen, H. J. ; Miller, B. L. ; Mintzer, J. ; Longmire, C. F. ; Spicer, K.

2020
Biomed Central London

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Please use a persistent id in citations: doi:10.1186/s13024-020-00407-2

Abstract: The Apolipoprotein E ε4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration.We included 708 subjects ranging from cognitively normal (CN, n = 221) to mild cognitive impairment (MCI, n = 414) and AD dementia (n = 73) from the Alzheimer's disease Neuroimaging Initiative. We used linear regression to test the interaction between ApoE4-carriage by CSF-assessed sTREM2 levels as a predictor of longitudinally assessed cognitive decline and MRI-assessed changes in hippocampal volume changes (mean follow-up of 4 years, range of 1.7-7 years).Across the entire sample, we found that higher CSF sTREM2 at baseline was associated with attenuated effects of ApoE4-carriage (i.e. sTREM2 x ApoE4 interaction) on longitudinal global cognitive (p = 0.001, Cohen's f2 = 0.137) and memory decline (p = 0.006, Cohen's f2 = 0.104) as well as longitudinally assessed hippocampal atrophy (p = 0.046, Cohen's f2 = 0.089), independent of CSF markers of primary AD pathology (i.e. Aβ1-42, p-tau181). While overall effects of sTREM2 were small, exploratory subanalyses stratified by diagnostic groups showed that beneficial effects of sTREM2 were pronounced in the MCI group.Our results suggest that a higher CSF sTREM2 levels are associated with attenuated ApoE4-related risk for future cognitive decline and AD-typical neurodegeneration. These findings provide further evidence that TREM2 may be protective against the development of AD.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Apolipoprotein E4: genetics (MeSH) ; Cognitive Dysfunction: cerebrospinal fluid (MeSH) ; Cognitive Dysfunction: genetics (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Female (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Membrane Glycoproteins: cerebrospinal fluid (MeSH) ; Nerve Degeneration: pathology (MeSH) ; Receptors, Immunologic (MeSH) ; Alzheimer’s disease ; ApoE4 ; Cognitive decline ; Microglial activation ; Neurodegeneration ; sTREM2

Note: ISSN 1750-1326 not unique: **3 hits**.

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Contributing Institute(s):

1. Clinical Neurodegeneration (AG Levin)
2. Molecular Neurodegeneration (AG Haass)
3. Molecular Neurobiology (AG Simons)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
3. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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