%0 Journal Article
%A Biel, Davina
%A Suarez-Calvet, Marc
%A Dewenter, Anna
%A Steward, Anna
%A Roemer, Sebastian N
%A Dehsarvi, Amir
%A Zhu, Zeyu
%A Pescoller, Julia
%A Frontzkowski, Lukas
%A Kreuzer, Annika
%A Haass, Christian
%A Schöll, Michael
%A Brendel, Matthias
%A Franzmeier, Nicolai
%T Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.
%J EMBO molecular medicine
%V 17
%N 2
%@ 1757-4676
%C [London]
%I Nature Publishing Group UK
%M DZNE-2025-00316
%P 235 - 248
%D 2025
%X In 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.
%K Humans
%K Alzheimer Disease: cerebrospinal fluid
%K Female
%K tau Proteins: cerebrospinal fluid
%K tau Proteins: metabolism
%K Membrane Glycoproteins: cerebrospinal fluid
%K Membrane Glycoproteins: metabolism
%K Receptors, Immunologic: metabolism
%K Aged
%K Male
%K Sex Factors
%K Cross-Sectional Studies
%K Amyloid beta-Peptides: cerebrospinal fluid
%K Amyloid beta-Peptides: metabolism
%K Aged, 80 and over
%K Apolipoprotein E4: genetics
%K Middle Aged
%K Alzheimer’s Disease (Other)
%K Microglia (Other)
%K Sex Differences (Other)
%K p-tau (Other)
%K sTREM2 (Other)
%K tau Proteins (NLM Chemicals)
%K TREM2 protein, human (NLM Chemicals)
%K Membrane Glycoproteins (NLM Chemicals)
%K Receptors, Immunologic (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Apolipoprotein E4 (NLM Chemicals)
%K MAPT protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39794447
%2 pmc:PMC11822105
%R 10.1038/s44321-024-00190-3
%U https://pub.dzne.de/record/276777