Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone
Year: 2020
Type: article
Abstract: 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.
Source: Biology of Sex Differences
Institution: University of California San Diego
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,790
Funders: U.S. Department of Defense, Foundation for the National Institutes of Health, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering
Awards: G1012222616, G104586243, G1298807586, G1554142629, G1593117279, G1650819308, G1823308732, G1880935189, Alzheimer's Disease Neuroimaging Initiative, G2100670906, G2105457377, G2152643862, G2189010064, G2191645356, G2319973588, G2340207221, G2423387114, G2471646051, G2484314121, G2522063444, G279072258, G2835601961, G2957681590, G29951154, G3130427885, G3131374986, G3146424788, G3216574877, G3553156159, G3705772492, G3710456697, G3752451908, G3870774570, G3908963977, G3966393351, G4119534169, G423967958, G43180419, G4401988282, G4475667458, G4501223628, G4800177743, G4860885537, G5207404921, G528601746, G5324093878, G5365730499, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", G5389965057, G5654639750, G5740349702, G5850682332, G613619302, G6210868510, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6948409098, G72415811, G7298697282, G7414321945, G764699806, G781725486, G8228018387, G8281378126, G839208290, G8513896556, G8852128998, G8895907669, G8897063270, G8957659042, G9000009473, G9000035441, G9000039018, G9000074849, G9000122335, G9000145764, G9000276430, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Alzheimer's Disease Neuroimaging Initiative (ADNI4), G920654007
OpenAlex ID: W3036330497