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From the Taub Alzheimer’s Disease Research Center (Drs. Mayeux, Honig, Tang, Manly, Stern, and Schupf), Gertrude H. Sergievsky Center (Drs. Mayeux, Tang, Manly, Stern, and Schupf), Departments of Neurology (Drs. Mayeux, Honig, Manly, and Stern) and Psychiatry (Drs. Mayeux and Stern), and Divisions of Epidemiology (Dr. Mayeux) and Biostatistics (Dr. Tang), School of Public Health, Columbia University, New York, and Laboratory of Epidemiology (Dr. Schupf) and Department of Immunology (Dr. Mehta), Institute for Basic Research in Developmental Disabilities, Staten Island, NY.
Address correspondence and reprint requests to Dr. R. Mayeux, Gertrude H. Sergievsky Center, Columbia University, 630 W. 168 St., New York, NY 10032; e-mail: rpm2{at}columbia.edu
Background: Plasma amyloid ß-peptide (Aß) 40 and Aß42 levels are increased in persons with mutations causing early-onset familial Alzheimer’s disease (AD). Plasma Aß42 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 Aß40 and Aß42 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 Aß40 and Aß42 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 Aß42, but not Aß40, plasma levels. The risk of AD in the highest quartile of plasma Aß42 was increased by more than twofold over that in the lowest quartile. The highest plasma Aß42 levels were observed in patients with AD who died during the follow-up. Plasma Aß42, but not Aß40, levels decreased over time in patients with newly acquired AD.
Conclusions: Plasma Aß40 and Aß42 increase with age and are strongly correlated with each other. Plasma Aß40 and Aß42 levels are elevated in some patients before and during the early stages of AD but decline thereafter. High plasma Aß42 levels may also be associated with mortality in patients with AD.
Received May 20, 2003. Accepted in final form July 26, 2003.
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