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From the Departments of Psychiatry and Neurology (O.L.L., J.T.B., R.A.S., S.T.D.), Epidemiology (L.H.K.), Psychology (J.T.B.), and Neurosurgery (Y.F.C.), University of Pittsburgh, PA; Institute for Basic Research in Developmental Disabilities (P.D.M.), Staten Island, NY; MR Research Imaging Facility (H.M.G.), Nevada Cancer Institute, Las Vegas, NV; Department of Health Physics (H.M.G.), University of Nevada, Las Vegas; and Department of Pathology (R.T.), University of Vermont, Colchester.
Address correspondence and reprint requests to Dr. Oscar L. Lopez, 3501 Forbes Ave., Suite 830, Pittsburgh, PA 15213 lopezol{at}upmc.edu
Objectives: To examine the association between incident Alzheimer disease (AD), and plasma Aβ1-40 and Aβ1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study.
Methods: We determined the plasma Aβ1-40 and Aβ1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998–1999 and repeated the measurements in 2002–2003. The mean age of the subjects at baseline was 79.3 ± 3.6 years. We examined the association between Aβ levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts.
Results: In an unadjusted prospective model in normal subjects, both Aβ1-40 and Aβ1-42 levels in 1998–1999 were associated with incident AD (n = 55) in 2002–2003 (longitudinal analysis). In the fully adjusted multivariate model, neither Aβ1-42 nor Aβ1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for Aβ1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002–2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD.
Conclusions: Plasma Aβ levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, Aβ-40 and Aβ1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of Aβ do not seem to be useful biomarkers for AD.
Abbreviations: 3MSE = Modified Mini-Mental State Examination; AD = Alzheimer disease; BSA = bovine serum albumin; CES-D = Center for Epidemiology Studies Depression Scale; CHS = Cardiovascular Health Study; CHSCS = Cardiovascular Health Study Cognition Study; IADL = instrumental activities of daily living; MCI = mild cognitive impairment; OD = optical density; OR = odds ratio; PBS = phosphate-buffered saline.
Supplemental data at www.neurology.org
e-Pub ahead of print on April 9, 2008, at www.neurology.org.
Supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01-HC-15103 from the National Heart, Lung, and Blood Institute and grants AG15928 and AG20098 from the National Institute on Aging.
Disclosure: The authors report no conflicts of interest.
Received July 30, 2007. Accepted in final form January 2, 2008.
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