Gene–Environment Interactions: Lifetime Cognitive Activity, APOE Genotype, and Beta-Amyloid Burden

摘要: Carriers of the apolipoprotein E (APOE) e4 allele, major genetic risk for Alzheimer's disease (AD), harbor an increased load β-amyloid (Aβ) plaque burden that is felt to be a instigator AD development. Data has suggested lifestyle factors may reduce by directly mitigating Aβ pathology, which could particularly beneficial in APOE carriers. We therefore examined interaction between lifetime cognitive activity and allele relation brain burden. obtained measures 118 cognitively normal human individuals (mean age: 76.13 ± 5.56 years, 70 women) using validated questionnaire included over early, middle, current age epochs. Hierarchical regression models (adjusted age, gender, years education) were conducted examine effects carrier status, activity, two with cortical deposition, quantified [11C] Pittsburgh-compound-B (PIB)-PET. As expected, carriers exhibited higher PIB retention compared noncarriers. Lifetime moderated genotype effect such was diminished reported life course. The findings suggest greater forestall specifically genetically susceptible individuals. imply training promotes neural efficiency might retard lifelong neurally mediated deposition Aβ.