Objective. To determine whether years of education and the ε4 risk allele at APOE influence β-amyloid pathology similarly in asymptomatic individuals with a family history of sporadic Alzheimer’s disease (AD) and pre-symptomatic autosomal dominant AD mutation carriers.

Methods. We analyzed cross-sectional data from 106 asymptomatic individuals with a parental history of sporadic AD (PREVENT-AD cohort; age=67.28±4.72 years) and 117 pre-symptomatic autosomal dominant AD mutation carriers (DIAN cohort; age=34.00±9.43 years). All participants underwent structural MRI and β-amyloid PET imaging. In each cohort we investigated the influence of years of education, APOE-ε4 status and their interaction on β-amyloid PET.

Results. Asymptomatic individuals with a parental history of sporadic AD showed increased β-amyloid burden associated with APOE-ε4 carriage and lower level of education, but no interaction between these. Pre-symptomatic mutation carriers of autosomal dominant AD showed no relation between APOE-ε4 and β-amyloid burden, but increasing level of education was associated with reduced β-amyloid burden. The association between educational attainment and β-amyloid burden was similar in the two cohorts.

Conclusions. While the APOE-ε4 allele confers increased tendency toward β-amyloid accumulation in sporadic AD only, protective environmental factors, like increased education, may promote brain resistance against β-amyloid pathology   in both sporadic and autosomal dominant AD.