A β1–40 but not A β1–42 levels in cortex correlate with apolipoprotein E ϵ4 allele dosage in sporadic Alzheimer's disease

Abstract

Apolipoprotein E (ApoE) ϵ4 allele is established to be a risk factor for the development of late-onset Alzheimer's disease (AD) which is associated with increased frequency of senile plaques and extent of amyloid angiopathy. In a recent report, we demonstrated that ApoE ϵ4 dosage correlates with an increase in A β1–40 but not A β1–42/43-immunoreactive plaques. In the present study, we sought to confirm this relationship at a biochemical level by using a sensitive ELISA to measure the amounts of A β1–42/43 and A β1–40 in cerebral cortex in 36 cases of sporadic AD. We found that dosage of ApoE ϵ4 allele correlated significantly with cortical A β1–40 levels, while levels of A β1–42 showed no significant association with genotype. These results parallel our immunohistochemical findings and suggest that A β1–40 may play a key role in the pathogenesis of late-onset sporadic AD.