Sex differences in Alzheimer's-related Tau biomarkers and a mediating effect of testosterone.
APOE
Alzheimer’s disease
Cerebrospinal fluid
Phosphorylated-Tau
Sex
Testosterone
Journal
Biology of sex differences
ISSN: 2042-6410
Titre abrégé: Biol Sex Differ
Pays: England
ID NLM: 101548963
Informations de publication
Date de publication:
19 06 2020
19 06 2020
Historique:
received:
17
04
2020
accepted:
12
06
2020
entrez:
21
6
2020
pubmed:
21
6
2020
medline:
6
7
2021
Statut:
epublish
Résumé
Women show greater pathological Tau biomarkers than men along the Alzheimer's disease (AD) continuum, particularly among apolipoprotein ε-E4 (APOE4) carriers; however, the reason for this sex difference in unknown. Sex differences often indicate an underlying role of sex hormones. We examined whether testosterone levels might influence this sex difference and the modifying role of APOE4 status. Analyses included 172 participants (25 cognitively normal, 97 mild cognitive impairment, 50 AD participants) from the Alzheimer's Disease Neuroimaging Initiative (34% female, 54% APOE4 carriers, aged 55-90). We examined the separate and interactive effects of plasma testosterone levels and APOE4 on cerebrospinal fluid phosphorylated-tau181 (p-Tau) levels in the overall sample and the sex difference in p-Tau levels before and after adjusting for testosterone. A significant APOE4-by-testosterone interaction revealed that lower testosterone levels related to higher p-Tau levels among APOE4 carriers regardless of sex. As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers.
Identifiants
pubmed: 32560743
doi: 10.1186/s13293-020-00310-x
pii: 10.1186/s13293-020-00310-x
pmc: PMC7304096
doi:
Substances chimiques
Apolipoprotein E4
0
Biomarkers
0
MAPT protein, human
0
SHBG protein, human
0
Sex Hormone-Binding Globulin
0
tau Proteins
0
Testosterone
3XMK78S47O
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
33Subventions
Organisme : NIH HHS
ID : AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062429
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG066088
Pays : United States
Organisme : NIH HHS
ID : AG05131
Pays : United States
Organisme : U.S. Department of Defense
ID : W81XWH-12-2-0012
Pays : International
Organisme : NIA NIH HHS
ID : R01 AG056410
Pays : United States
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