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 (Aβ 42 ), phospho-tau-181 (p-tau 181 ), 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-tau 181 increased with age over the adult life span ( p < 0.01) with no gender differences in those increases. CSF Aβ 42 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.