Hohman TJ, et al. - Experts assessed the sex differences in the correlation between apolipoprotein E (APOE) and markers of Alzheimer disease (AD) neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy. Across multiple independent data sets, a stronger correlation was discovered between APOE-ε4 and CSF tau levels among women vs men. It was noted that APOE-ε4 was not differentially linked with autopsy measures of neurofibrillary tangles. According to the results, APOE could modulate risk for neurodegeneration in a sex-specific manner, especially in the presence of amyloidosis. This was indicated by the sex difference in the connection between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy.

Methods

• Data was extracted from 10 longitudinal cohort studies of normal aging and AD.
• Cohorts presented with different recruitment criteria and follow-up intervals and included population-based and clinic-based samples.
• Inclusion criteria involved APOE genotype data and either CSF data available for analysis.
• Analyses initiated on November 6, 2017, and were completed on December 20, 2017.
• Biomarker analyses included levels of β-amyloid 42, total tau, and phosphorylated tau measured in CSF, and served as the primary outcome.
• Autopsy analyses consisted of Consortium to Establish a Registry for Alzheimer disease staging for neuritic plaques and Braak staging for neurofibrillary tangles.

Results

• Among 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1,690 were white, and the mean (SD) age was 70 (9) years.
• Out of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean (SD) age was 84 (9) years.
• A statistically significant interaction was found between APOE-ε4 and sex on CSF total tau (β = 0.41; 95% CI, 0.27-0.55; P < .001) and phosphorylated tau (β = 0.24; 95% CI, 0.09-0.38; P=.001) after correcting for multiple comparisons using the Bonferroni procedure.
• APOE demonstrated a stronger relation among women than men.
• As per the post hoc analyses, this sex difference was found among amyloid-positive individuals (β = 0.41; 95% CI, 0.20-0.62; P < .001) but not among amyloid-negative individuals (β = 0.06; 95% CI, -0.18 to 0.31; P=.62).
• No sex differences were reported in the correlation between APOE and β-amyloid 42, neuritic plaque burden, or neurofibrillary tangle burden.