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000276777 041__ $$aEnglish
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000276777 1001_ $$00000-0002-2597-1992$$aBiel, Davina$$b0
000276777 245__ $$aFemale sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.
000276777 260__ $$a[London]$$bNature Publishing Group UK$$c2025
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000276777 520__ $$aIn Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau181 determined in the cerebrospinal fluid (CSF). To assess potentially modulating effects of female sex, younger age, and ApoE4, we included 322 ADNI participants with cross-sectional/longitudinal p-tau181. To determine effects of microglial activation on p-tau181, we included 454 subjects with cross-sectional CSF sTREM2. Running ANCOVAs for nominal and linear regressions for metric variables, we found that women had higher Aβ-related p-tau181 levels. Higher sTREM2 was associated with elevated p-tau181, with stronger associations in women. Similarly, ApoE4 was related to higher p-tau181 levels and faster p-tau181 increases, with stronger effects in female ApoE4 carriers. Our results show that sex alone modulates the Aβ to p-tau axis, where women show higher Aβ-dependent p-tau secretion, potentially driven by elevated sTREM2-related microglial activation and stronger effects of ApoE4 carriership in women.
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000276777 650_7 $$2Other$$aAlzheimer’s Disease
000276777 650_7 $$2Other$$aMicroglia
000276777 650_7 $$2Other$$aSex Differences
000276777 650_7 $$2Other$$ap-tau
000276777 650_7 $$2Other$$asTREM2
000276777 650_7 $$2NLM Chemicals$$atau Proteins
000276777 650_7 $$2NLM Chemicals$$aTREM2 protein, human
000276777 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000276777 650_7 $$2NLM Chemicals$$aReceptors, Immunologic
000276777 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000276777 650_7 $$2NLM Chemicals$$aApolipoprotein E4
000276777 650_7 $$2NLM Chemicals$$aMAPT protein, human
000276777 650_2 $$2MeSH$$aHumans
000276777 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000276777 650_2 $$2MeSH$$aFemale
000276777 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000276777 650_2 $$2MeSH$$atau Proteins: metabolism
000276777 650_2 $$2MeSH$$aMembrane Glycoproteins: cerebrospinal fluid
000276777 650_2 $$2MeSH$$aMembrane Glycoproteins: metabolism
000276777 650_2 $$2MeSH$$aReceptors, Immunologic: metabolism
000276777 650_2 $$2MeSH$$aAged
000276777 650_2 $$2MeSH$$aMale
000276777 650_2 $$2MeSH$$aSex Factors
000276777 650_2 $$2MeSH$$aCross-Sectional Studies
000276777 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000276777 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000276777 650_2 $$2MeSH$$aAged, 80 and over
000276777 650_2 $$2MeSH$$aApolipoprotein E4: genetics
000276777 650_2 $$2MeSH$$aMiddle Aged
000276777 7001_ $$0P:(DE-2719)2811727$$aSuarez-Calvet, Marc$$b1
000276777 7001_ $$aDewenter, Anna$$b2
000276777 7001_ $$00000-0002-8438-3760$$aSteward, Anna$$b3
000276777 7001_ $$00000-0003-3423-457X$$aRoemer, Sebastian N$$b4
000276777 7001_ $$00000-0001-7116-9741$$aDehsarvi, Amir$$b5
000276777 7001_ $$aZhu, Zeyu$$b6
000276777 7001_ $$aPescoller, Julia$$b7
000276777 7001_ $$aFrontzkowski, Lukas$$b8
000276777 7001_ $$aKreuzer, Annika$$b9
000276777 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b10
000276777 7001_ $$00000-0001-7800-1781$$aSchöll, Michael$$b11
000276777 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b12$$eLast author$$udzne
000276777 7001_ $$00000-0001-9736-2283$$aFranzmeier, Nicolai$$b13
000276777 773__ $$0PERI:(DE-600)2485479-7$$a10.1038/s44321-024-00190-3$$gVol. 17, no. 2, p. 235 - 248$$n2$$p235 - 248$$tEMBO molecular medicine$$v17$$x1757-4676$$y2025
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