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Abstract
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.
Glossary
- 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.
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