Plasma p‐tau217 and APOE genotype: Prodromal Alzheimer's disease staging

Introduction Plasma phosphorylated tau (p‐tau)217 levels and apolipoprotein E ( APOE ) ε4 genotype are used for prodromal identification of individuals at high risk for dementia. We used baseline samples from cognitively normal subjects in the Risk Reduction for Alzheimer's Disease (rrAD) clinical trial (NCT02913664) to investigate the relationship between these two markers in older adults with additional vascular risk factors. Methods We measured APOE genotype, plasma p‐tau217, and standard neuroimaging metrics in 400 rrAD participants, aged 60 to 84 years, with sedentary lifestyle, hypertension, and hypercholesterolemia. Results Plasma p‐tau217 was 57% higher in subjects with at least one APOE ε4 allele, increased with age, was higher in males, and negatively correlated with brain volume measures by magnetic resonance imaging. Discussion Plasma p‐tau217 demonstrated elevation in the APOE ε4 genotype in cognitively normal older adults. These data also suggest that brain volume shrinkage in males is related to elevated p‐tau217. APOE genotyping will be important for clinical practice using p‐tau217 quantification.