Association of education with Aβ burden in preclinical familial and sporadic Alzheimer disease

Neurology. 2020 Sep 15;95(11):e1554-e1564. doi: 10.1212/WNL.0000000000010314. Epub 2020 Aug 5.


Objective: To determine whether years of education and the ε4 risk allele at APOE influence β-amyloid (Aβ) pathology similarly in asymptomatic individuals with a family history of sporadic Alzheimer disease (AD) and presymptomatic 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 presymptomatic autosomal dominant AD mutation carriers (DIAN cohort; age 35.04 ± 9.43 years). All participants underwent structural MRI and Aβ-PET imaging. In each cohort we investigated the influence of years of education, APOE ε4 status, and their interaction on Aβ-PET.

Results: Asymptomatic individuals with a parental history of sporadic AD showed increased Aβ burden associated with APOE ε4 carriage and lower level of education, but no interaction between these. Presymptomatic mutation carriers of autosomal dominant AD showed no relation between APOE ε4 and Aβ burden, but increasing level of education was associated with reduced Aβ burden. The association between educational attainment and Aβ burden was similar in the 2 cohorts.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / genetics*
  • Amyloid beta-Peptides / metabolism
  • Apolipoprotein E4 / genetics*
  • Cohort Studies
  • Cross-Sectional Studies
  • Educational Status*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Young Adult


  • Amyloid beta-Peptides
  • Apolipoprotein E4