APOE ε4 carrier status modifies plasma p‐tau181 concentrations in cognitively healthy super‐seniors

INTRODUCTION This study investigates the effect of apolipoprotein E ( APOE ) genotype on neurology plasma biomarkers in cognitively healthy Super‐Seniors. METHODS Three hundred seventy plasma specimens from Super‐Senior participants ≥ 85 years old, who have never been diagnosed with dementia, cancer, diabetes, cardiovascular, or major pulmonary disease, were analyzed on the Quanterix Simoa HD‐X analyzer using commercial Neurology 4‐plex E and phosphorylated tau (p‐tau)181 assays. RESULTS Eighty (22%) participants were APOE ε4 carriers and 290 (73%) were non‐carriers. No significant differences were found between APOE ε4 carriers and non‐carriers regarding age, sex, or Mini‐Mental State Examination scores. In APOE ε4 carriers, plasma amyloid beta 42/40 was lower and p‐tau181 and glial fibrillary acidic protein were higher compared to non‐ APOE ε4 carriers. After adjusting for demographic variables, p‐tau181 was the only biomarker to remain significantly associated with APOE ε4 carrier status. DISCUSSION APOE ε4 genotype modifies plasma p‐tau181 concentration in seniors resilient to age‐related clinical disease, suggesting that some Super‐Seniors may have Alzheimer's disease pathology without progressing to cognitive decline. Highlights Healthy seniors enable identification of associations that may be masked by disease. Plasma phosphorylated tau (p‐tau)181 concentrations associate with apolipoprotein E ( APOE ) ε4 carriership in healthy seniors. APOE should be accounted for when interpreting p‐tau181, regardless of disease.