학술논문
Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau
Document Type
article
Author
Hohman, Timothy J; Dumitrescu, Logan; Barnes, Lisa L; Thambisetty, Madhav; Beecham, Gary; Kunkle, Brian; Gifford, Katherine A; Bush, William S; Chibnik, Lori B; Mukherjee, Shubhabrata; De Jager, Philip L; Kukull, Walter; Crane, Paul K; Resnick, Susan M; Keene, C Dirk; Montine, Thomas J; Schellenberg, Gerard D; Haines, Jonathan L; Zetterberg, Henrik; Blennow, Kaj; Larson, Eric B; Johnson, Sterling C; Albert, Marilyn; Bennett, David A; Schneider, Julie A; Jefferson, Angela L
Source
JAMA Neurology. 75(8)
Subject
Language
Abstract
ImportanceThe strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neuropathology in a sex-specific manner.ObjectiveTo evaluate sex differences in the association between APOE and markers of AD neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy.Design, setting, and participantsThis multicohort study selected data from 10 longitudinal cohort studies of normal aging and AD. Cohorts had variable recruitment criteria and follow-up intervals and included population-based and clinic-based samples. Inclusion in our analysis required APOE genotype data and either CSF data available for analysis. Analyses began on November 6, 2017, and were completed on December 20, 2017.Main outcomes and measuresBiomarker analyses included levels of β-amyloid 42, total tau, and phosphorylated tau measured in CSF. Autopsy analyses included Consortium to Establish a Registry for Alzheimer's Disease staging for neuritic plaques and Braak staging for neurofibrillary tangles.ResultsOf the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years. Of the 5109 patients in the autopsy cohort, 2813 were women, 4953 were white, and the mean (SD) age was 84 (9) years. After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β = 0.41; 95% CI, 0.27-0.55; P