TY  - JOUR
AU  - Biel, Davina
AU  - Suarez-Calvet, Marc
AU  - Dewenter, Anna
AU  - Steward, Anna
AU  - Roemer, Sebastian N
AU  - Dehsarvi, Amir
AU  - Zhu, Zeyu
AU  - Pescoller, Julia
AU  - Frontzkowski, Lukas
AU  - Kreuzer, Annika
AU  - Haass, Christian
AU  - Schöll, Michael
AU  - Brendel, Matthias
AU  - Franzmeier, Nicolai
TI  - Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.
JO  - EMBO molecular medicine
VL  - 17
IS  - 2
SN  - 1757-4676
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2025-00316
SP  - 235 - 248
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Female
KW  - tau Proteins: cerebrospinal fluid
KW  - tau Proteins: metabolism
KW  - Membrane Glycoproteins: cerebrospinal fluid
KW  - Membrane Glycoproteins: metabolism
KW  - Receptors, Immunologic: metabolism
KW  - Aged
KW  - Male
KW  - Sex Factors
KW  - Cross-Sectional Studies
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Amyloid beta-Peptides: metabolism
KW  - Aged, 80 and over
KW  - Apolipoprotein E4: genetics
KW  - Middle Aged
KW  - Alzheimer’s Disease (Other)
KW  - Microglia (Other)
KW  - Sex Differences (Other)
KW  - p-tau (Other)
KW  - sTREM2 (Other)
KW  - tau Proteins (NLM Chemicals)
KW  - TREM2 protein, human (NLM Chemicals)
KW  - Membrane Glycoproteins (NLM Chemicals)
KW  - Receptors, Immunologic (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Apolipoprotein E4 (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39794447
C2  - pmc:PMC11822105
DO  - DOI:10.1038/s44321-024-00190-3
UR  - https://pub.dzne.de/record/276777
ER  -