Plasma Aβ40 and Aβ42 and Alzheimer's disease -: Relation to age, mortality, and risk

Background: Plasma amyloid beta-peptide (Abeta) 40 and Abeta42 levels are increased in persons with mutations causing early-onset familial Alzheimer's disease (AD). Plasma Abeta42 levels were also used to link microsatellite genetic markers to a putative AD genetic locus on chromosome 10 and were observed in patients with incipient sporadic AD. Methods: The authors measured plasma Abeta40 and Abeta42 levels using a sandwich ELISA after the initial examination of 530 individuals participating in an epidemiologic study of aging and dementia. Participants were examined at 18-month intervals, and plasma Abeta40 and Abeta42 levels were repeated in 307 subjects 3 years after baseline. Results: Compared with individuals who never developed AD, patients with AD at baseline and those who developed AD during the follow-up had significantly higher Abeta42, but not Abeta40, plasma levels. The risk of AD in the highest quartile of plasma Abeta42 was increased by more than twofold over that in the lowest quartile. The highest plasma Abeta42 levels were observed in patients with AD who died during the follow-up. Plasma Abeta42, but not Abeta40, levels decreased over time in patients with newly acquired AD. Conclusions: Plasma Abeta40 and Abeta42 increase with age and are strongly correlated with each other. Plasma Abeta40 and Abeta42 levels are elevated in some patients before and during the early stages of AD but decline thereafter. High plasma Abeta42 levels may also be associated with mortality in patients with AD.