Plasma A[beta]40 and A[beta]42 and Alzheimer's disease: relation to age, mortality, and risk.
BACKGROUND
Plasma amyloid [beta]-peptide (A[beta]) 40 and A[beta]42 levels are increased in persons with mutations causing early-onset familial Alzheimer's disease (AD). Plasma A[beta]42 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 A[beta]40 and A[beta]42 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 A[beta]40 and A[beta]42 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 A[beta]42, but not A[beta]40, plasma levels. The risk of AD in the highest quartile of plasma A[beta]42 was increased by more than twofold over that in the lowest quartile. The highest plasma A[beta]42 levels were observed in patients with AD who died during the follow-up. Plasma A[beta]42, but not A[beta]40, levels decreased over time in patients with newly acquired AD.


CONCLUSIONS
Plasma A[beta]40 and A[beta]42 increase with age and are strongly correlated with each other. Plasma A[beta]40 and A[beta]42 levels are elevated in some patients before and during the early stages of AD but decline thereafter. High plasma A[beta]42 levels may also be associated with mortality in patients with AD.
Mayeux
R
R
Taub Alzheimer's Disease Research Center, School of Public Health, Columbia University, New York, NY 10032, USA.
Honig
L S
LS
Tang
M-X
MX
Manly
J
J
Stern
Y
Y
Schupf
N
N
Mehta
P D
PD
D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics / Q000401:mortality*; D016229:Amyloid beta-Peptides / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D009519:New York City / Q000453:epidemiology; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D008055:Lipids; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)