Journal Article

DZNE-2025-00316

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.

Biel, D. ; Suarez-Calvet, M. ; Dewenter, A. ; Steward, A. ; Roemer, S. N. ; Dehsarvi, A. ; Zhu, Z. ; Pescoller, J. ; Frontzkowski, L. ; Kreuzer, A. ; Haass, C.DZNE* ; Schöll, M. ; Brendel, M. (Last author)DZNE* ; Franzmeier, N.

2025
Nature Publishing Group UK [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s44321-024-00190-3

Abstract: 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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Female (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; tau Proteins: metabolism (MeSH) ; Membrane Glycoproteins: cerebrospinal fluid (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Aged (MeSH) ; Male (MeSH) ; Sex Factors (MeSH) ; Cross-Sectional Studies (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Aged, 80 and over (MeSH) ; Apolipoprotein E4: genetics (MeSH) ; Middle Aged (MeSH) ; Alzheimer’s Disease ; Microglia ; Sex Differences ; p-tau ; sTREM2 ; tau Proteins ; TREM2 protein, human ; Membrane Glycoproteins ; Receptors, Immunologic ; Amyloid beta-Peptides ; Apolipoprotein E4 ; MAPT protein, human

---

Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Wiley ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---