Cerebrospinal fluid biomarkers for Alzheimer's and vascular disease vary by age, gender, and APOE genotype in cognitively normal adults

Background: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults. Methods: CSF amyloid beta_1-42 (Aβ₄₂), phospho-Tau-181 (p-Tau₁₈₁), and total tau were measured in 331 participants who were between the ages of 21 and 100. CSF E-selectin and vascular cell adhesion protein 1 (VCAM1) were measured in 249 participants who were between the ages of 50 and 100. Results: CSF total tau and p-Tau₁₈₁ increased with age over the adult life span (p < 0.01) with no gender differences in those increases. CSF Aβ₄₂ concentration varied according to age, gender, and APOE genotype (interaction of age × gender × ϵ4, p = 0.047). CSF VCAM1, but not E-selectin, increased with age (p < 0.01), but both were elevated in men compared to women (p < 0.01). Conclusions: Female APOE-ϵ4 carriers appear at higher risk for AD after age 50. In contrast, men may experience a relatively higher rate of cerebrovascular injury in middle and early old age.