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

ObjectiveTo 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.MethodsWe 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.ResultsAsymptomatic 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.ConclusionsWhile 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.

The Erythrocytic Hypothesis of Brain Energy Crisis in Sporadic Alzheimer Disease: Possible Consequences and Supporting Evidence

Alzheimer’s disease (AD) is a fatal form of dementia of unknown etiology. Although amyloid plaque accumulation in the brain has been the subject of intensive research in disease pathogenesis and anti-amyloid drug development; the continued failures of the clinical trials suggest that amyloids are not a key cause of AD and new approaches to AD investigation and treatment are needed. We propose a new hypothesis of AD development based on metabolic abnormalities in circulating red blood cells (RBCs) that slow down oxygen release from RBCs into brain tissue which in turn leads to hypoxia-induced brain energy crisis; loss of neurons; and progressive atrophy preceding cognitive dysfunction. This review summarizes current evidence for the erythrocytic hypothesis of AD development and provides new insights into the causes of neurodegeneration offering an innovative way to diagnose and treat this systemic disease.