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@ARTICLE{Franzmeier:154370,
author = {Franzmeier, Nicolai and Suárez-Calvet, M. and
Frontzkowski, Lukas and Moore, Annah and Hohman, Timothy J
and Morenas-Rodriguez, Estrella and Nuscher, Brigitte and
Shaw, Leslie and Trojanowski, John Q and Dichgans, Martin
and Kleinberger, Gernot and Haass, Christian and Ewers,
Michael and Weiner, Michael and Aisen, Paul and Novak,
Gerald and Green, Robert C and Montine, Tom and Petersen,
Ronald and Gamst, Anthony and Thomas, Ronald G and Donohue,
Michael and Walter, Sarah and Gessert, Devon and Sather,
Tamie and Beckett, Laurel and Harvey, Danielle and Kornak,
John and Jack, Clifford R and Dale, Anders and Bernstein,
Matthew and Felmlee, Joel and Fox, Nick and Thompson, Paul
and Schuff, Norbert and Alexander, Gene and DeCarli, Charles
and Jagust, William and Bandy, Dan and Koeppe, Robert A and
Foster, Norm and Reiman, Eric M and Chen, Kewei and Mathis,
Chet and Morris, John and Cairns, Nigel J and
Taylor-Reinwald, Lisa and Trojanowki, J. Q. and Shaw, Les
and Lee, Virginia M Y and Korecka, Magdalena and Toga,
Arthur W and Crawford, Karen and Neu, Scott and Saykin,
Andrew J and Foroud, Tatiana M and Potkin, Steven and Shen,
Li and Kachaturian, Zaven and Frank, Richard and Snyder,
Peter J and Molchan, Susan and Kaye, Jeffrey and Dolen, Sara
and Quinn, Joseph and Schneider, Lon S and Pawluczyk, Sonia
and Spann, Bryan M and Brewer, James and Vanderswag, Helen
and Heidebrink, Judith L and Lord, Joanne L and Johnson,
Kris and Doody, Rachelle S and Villanueva-Meyer, Javier and
Chowdhury, Munir and Stern, Yaakov and Honig, Lawrence S and
Bell, Karen L and Morris, John C and Mintun, Mark A and
Schneider, Stacy and Marson, Daniel and Griffith, Randall
and Clark, David and Grossman, Hillel and Mitsis, Effie and
Romirowsky, Aliza and deToledo-Morrell, Leyla and Shah, Raj
C and Duara, Ranjan and Varon, Daniel and Roberts, Peggy and
Albert, Marilyn and Onyike, Chiadi and Kielb, Stephanie and
Rusinek, Henry and de Leon, Mony J and Glodzik, Lidia and
Doraiswamy, P Murali and Petrella, Jeffrey R and Arnold,
Steven E and Karlawish, Jason H and Wolk, David and Smith,
Charles D and Jicha, Greg and Hardy, Peter and Lopez, Oscar
L and Oakley, Mary Ann and Simpson, Donna M and Ismail, M
Saleem and Brand, Connie and Mulnard, Ruth A and Thai, Gaby
and Mc-Adams-Ortiz, Catherine and Diaz-Arrastia, Ramon and
Martin-Cook, Kristen and DeVous, Michael and Levey, Allan I
and Lah, James J and Cellar, Janet S and Burns, Jeffrey M
and Anderson, Heather S and Swerdlow, Russell H and
Bartzokis, George and Silverman, Daniel H S and Lu, Po H and
Apostolova, Liana and Graff-Radford, Neill R and Parfitt,
Francine and Johnson, Heather and Farlow, Martin and
Herring, Scott and Hake, Ann M and van Dyck, Christopher H
and Carson, Richard E and MacAvoy, Martha G and Chertkow,
Howard and Bergman, Howard and Hosein, Chris and Black,
Sandra and Stefanovic, Bojana and Caldwell, Curtis and
Hsiung, Ging-Yuek Robin and Feldman, Howard and Assaly,
Michele and Kertesz, Andrew and Rogers, John and Trost, Dick
and Bernick, Charles and Munic, Donna and Wu, Chuang-Kuo and
Johnson, Nancy and Mesulam, Marsel and Sadowsky, Carl and
Martinez, Walter and Villena, Teresa and Turner, Raymond
Scott and Johnson, Kathleen and Reynolds, Brigid and
Sperling, Reisa A and Frey, Meghan and Johnson, Keith A and
Rosen, Allyson and Tinklenberg, Jared and Ashford, Wes and
Sabbagh, Marwan and Belden, Christine and Jacobson, Sandra
and Killiany, Ronald and Norbash, Alexander and Nair, Anil
and Obisesan, Thomas O and Wolday, Saba and Bwayo, Salome K
and Lerner, Alan and Hudson, Leon and Ogrocki, Paula and
Fletcher, Evan and Carmichael, Owen and Kittur, Smita and
Borrie, Michael and Lee, T-Y and Bartha, Rob and Johnson,
Sterling and Asthana, Sanjay and Carlsson, Cynthia M and
Potkin, Steven G and Preda, Adrian and Nguyen, Dana and
Tariot, Pierre and Fleisher, Adam and Reeder, Stephanie and
Bates, Vernice and Capote, Horacio and Rainka, Michelle and
Hendin, Barry A and Scharre, Douglas W and Kataki, Maria and
Zimmerman, Earl A and Celmins, Dzintra and Brown, Alice D
and Hosp, Hartford and Pearlson, Godfrey D and Blank, Karen
and Anderson, Karen and Santulli, Robert B and Schwartz,
Eben S and Williamson, Jeff D and Sink, Kaycee M and
Watkins, Franklin and Ott, Brian R and Querfurth, Henry and
Tremont, Geoffrey and Salloway, Stephen and Malloy, Paul and
Correia, Stephen and Rosen, Howard J and Miller, Bruce L and
Mintzer, Jacobo and Longmire, Crystal Flynn and Spicer,
Kenneth},
collaboration = {Initiative, Alzheimer’s Disease Neuroimaging},
title = {{H}igher {CSF} s{TREM}2 attenuates {A}po{E}4-related risk
for cognitive decline and neurodegeneration.},
journal = {Molecular neurodegeneration},
volume = {15},
number = {1},
issn = {1750-1326},
address = {London},
publisher = {Biomed Central},
reportid = {DZNE-2021-00223},
pages = {57},
year = {2020},
note = {ISSN 1750-1326 not unique: **3 hits**.},
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.},
keywords = {Aged / Aged, 80 and over / Alzheimer Disease: cerebrospinal
fluid / Alzheimer Disease: genetics / Alzheimer Disease:
pathology / Apolipoprotein E4: genetics / Cognitive
Dysfunction: cerebrospinal fluid / Cognitive Dysfunction:
genetics / Cognitive Dysfunction: pathology / Female /
Genetic Predisposition to Disease / Humans / Male / Membrane
Glycoproteins: cerebrospinal fluid / Nerve Degeneration:
pathology / Receptors, Immunologic / Alzheimer’s disease
(Other) / ApoE4 (Other) / Cognitive decline (Other) /
Microglial activation (Other) / Neurodegeneration (Other) /
sTREM2 (Other)},
cin = {AG Levin / AG Haass / AG Simons},
ddc = {570},
cid = {I:(DE-2719)1111016 / I:(DE-2719)1110007 /
I:(DE-2719)1110008},
pnm = {341 - Molecular Signaling (POF3-341) / 342 - Disease
Mechanisms and Model Systems (POF3-342) / 344 - Clinical and
Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-341 / G:(DE-HGF)POF3-342 /
G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33032659},
pmc = {pmc:PMC7545547},
doi = {10.1186/s13024-020-00407-2},
url = {https://pub.dzne.de/record/154370},
}
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