000154370 001__ 154370
000154370 005__ 20240411115843.0
000154370 0247_ $$2doi$$a10.1186/s13024-020-00407-2
000154370 0247_ $$2pmid$$apmid:33032659
000154370 0247_ $$2pmc$$apmc:PMC7545547
000154370 0247_ $$2altmetric$$aaltmetric:92036329
000154370 037__ $$aDZNE-2021-00223
000154370 041__ $$aEnglish
000154370 082__ $$a570
000154370 1001_ $$00000-0001-9736-2283$$aFranzmeier, Nicolai$$b0
000154370 245__ $$aHigher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.
000154370 260__ $$aLondon$$bBiomed Central$$c2020
000154370 3367_ $$2DRIVER$$aarticle
000154370 3367_ $$2DataCite$$aOutput Types/Journal article
000154370 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1712750767_11352
000154370 3367_ $$2BibTeX$$aARTICLE
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000154370 3367_ $$00$$2EndNote$$aJournal Article
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000154370 520__ $$aThe 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.
000154370 536__ $$0G:(DE-HGF)POF3-341$$a341 - Molecular Signaling (POF3-341)$$cPOF3-341$$fPOF III$$x0
000154370 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x1
000154370 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x2
000154370 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000154370 650_7 $$2Other$$aAlzheimer’s disease
000154370 650_7 $$2Other$$aApoE4
000154370 650_7 $$2Other$$aCognitive decline
000154370 650_7 $$2Other$$aMicroglial activation
000154370 650_7 $$2Other$$aNeurodegeneration
000154370 650_7 $$2Other$$asTREM2
000154370 650_2 $$2MeSH$$aAged
000154370 650_2 $$2MeSH$$aAged, 80 and over
000154370 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000154370 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000154370 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000154370 650_2 $$2MeSH$$aApolipoprotein E4: genetics
000154370 650_2 $$2MeSH$$aCognitive Dysfunction: cerebrospinal fluid
000154370 650_2 $$2MeSH$$aCognitive Dysfunction: genetics
000154370 650_2 $$2MeSH$$aCognitive Dysfunction: pathology
000154370 650_2 $$2MeSH$$aFemale
000154370 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000154370 650_2 $$2MeSH$$aHumans
000154370 650_2 $$2MeSH$$aMale
000154370 650_2 $$2MeSH$$aMembrane Glycoproteins: cerebrospinal fluid
000154370 650_2 $$2MeSH$$aNerve Degeneration: pathology
000154370 650_2 $$2MeSH$$aReceptors, Immunologic
000154370 7001_ $$aSuárez-Calvet, M.$$b1
000154370 7001_ $$aFrontzkowski, Lukas$$b2
000154370 7001_ $$aMoore, Annah$$b3
000154370 7001_ $$aHohman, Timothy J$$b4
000154370 7001_ $$aMorenas-Rodriguez, Estrella$$b5
000154370 7001_ $$aNuscher, Brigitte$$b6
000154370 7001_ $$aShaw, Leslie$$b7
000154370 7001_ $$aTrojanowski, John Q$$b8
000154370 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b9$$udzne
000154370 7001_ $$0P:(DE-HGF)0$$aKleinberger, Gernot$$b10
000154370 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b11$$udzne
000154370 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b12$$eLast author$$udzne
000154370 7001_ $$0P:(DE-HGF)0$$aInitiative, Alzheimer’s Disease Neuroimaging$$b13$$eCollaboration Author
000154370 7001_ $$aWeiner, Michael$$b14
000154370 7001_ $$aAisen, Paul$$b15
000154370 7001_ $$aNovak, Gerald$$b16
000154370 7001_ $$aGreen, Robert C$$b17
000154370 7001_ $$aMontine, Tom$$b18
000154370 7001_ $$aPetersen, Ronald$$b19
000154370 7001_ $$aGamst, Anthony$$b20
000154370 7001_ $$aThomas, Ronald G$$b21
000154370 7001_ $$aDonohue, Michael$$b22
000154370 7001_ $$aWalter, Sarah$$b23
000154370 7001_ $$aGessert, Devon$$b24
000154370 7001_ $$aSather, Tamie$$b25
000154370 7001_ $$aBeckett, Laurel$$b26
000154370 7001_ $$aHarvey, Danielle$$b27
000154370 7001_ $$aKornak, John$$b28
000154370 7001_ $$aJack, Clifford R$$b29
000154370 7001_ $$aDale, Anders$$b30
000154370 7001_ $$aBernstein, Matthew$$b31
000154370 7001_ $$aFelmlee, Joel$$b32
000154370 7001_ $$aFox, Nick$$b33
000154370 7001_ $$aThompson, Paul$$b34
000154370 7001_ $$aSchuff, Norbert$$b35
000154370 7001_ $$aAlexander, Gene$$b36
000154370 7001_ $$aDeCarli, Charles$$b37
000154370 7001_ $$aJagust, William$$b38
000154370 7001_ $$aBandy, Dan$$b39
000154370 7001_ $$aKoeppe, Robert A$$b40
000154370 7001_ $$aFoster, Norm$$b41
000154370 7001_ $$aReiman, Eric M$$b42
000154370 7001_ $$aChen, Kewei$$b43
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000154370 7001_ $$aCairns, Nigel J$$b46
000154370 7001_ $$aTaylor-Reinwald, Lisa$$b47
000154370 7001_ $$aTrojanowki, J. Q.$$b48
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000154370 773__ $$0PERI:(DE-600)2244557-2$$a10.1186/s13024-020-00407-2$$gVol. 15, no. 1, p. 57$$n1$$p57$$tMolecular neurodegeneration$$v15$$x1750-1326$$y2020
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