APOE genotypes are associated with the level of naturally occurring antibodies to amyloid-β in patients with Alzheimer's disease.

Apolipoprotein E ε4 (APOEε4) allele is the strongest known genetic risk factor for Alzheimer's disease (AD). Mechanisms underlying this association are incompletely understood. We aimed to determine whether APOE genotypes influenced the level of naturally occurring antibodies to amyloid-β (Aβ), a hallmark of AD, and whether anti-Aβ antibodies contributed to neurodegeneration, as measured by mini-mental state examination (MMSE) score. The study population consisted of 93 Italian AD patients. Results showed that APOEε4-carriers had significantly higher levels of anti-Aβ antibodies than non-carriers (p = 0.018). After adjusting for age, sex, Aβ levels in serum, and the MMSE scores, regression analyses showed marginal association between APOEε4 carrier status and the levels of anti-Aβ antibodies (p = 0.050). This is the first report of its kind and needs to be confirmed in a large multiethnic population.