A beta 1-40 but not A beta 1-42 levels in cortex correlate with apolipoprotein E epsilon 4 allele dosage in sporadic Alzheimer's disease

Apolipoprotein E (ApoE) is an element of 4 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 is an element of 4 dosage correlates with an increase in A beta 1-40 but not A beta 1-42/43-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 beta 1-42/43 and A beta 1-40 in cerebral cortex in 36 cases of sporadic AD. We found that dosage of ApoE is an element of 4 allele correlated significantly with cortical A beta 1-40 levels, while levels of A beta 1-42 showed no significant association with genotype. These results parallel our immunohistochemical findings and suggest that A beta 1-40 may play a key role in the pathogenesis of late-onset sporadic AD.