Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study.

Abstract

OBJECTIVES:

To examine the association between incident Alzheimer disease (AD), and plasma A beta 1-40 and A beta 1-42 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 A beta 1-40 and A beta 1-42 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 A beta 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 A beta 1-40 and A beta 1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither A beta 1-42 nor A beta 1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for A beta 1-42, 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 A beta levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, A beta-40 and A beta 1-42 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 A beta do not seem to be useful biomarkers for AD.

• Authors: O L Lopez, L H Kuller, P D Mehta, J T Becker, H M Gach, R A Sweet, Y F Chang, R Tracy, S T DeKosky
• Journal: Neurology (Neurology) Vol. 70 Issue 19 Pg. 1664-71 (May 06 2008) ISSN: 1526-632X [Electronic] United States
• PMID: 18401021 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amyloid beta-Peptides
• Apolipoprotein E4
• Biomarkers
• CST3 protein, human
• Cystatin C
• Cystatins
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Alzheimer Disease (blood, epidemiology, physiopathology)
• Amyloid beta-Peptides (blood)
• Apolipoprotein E4 (genetics)
• Biomarkers (analysis, blood)
• Brain (metabolism, pathology, physiopathology)
• Cerebrovascular Disorders (epidemiology)
• Comorbidity
• Cross-Sectional Studies
• Cystatin C
• Cystatins (blood)
• Female
• Humans
• Incidence
• Longitudinal Studies
• Magnetic Resonance Imaging
• Male
• Models, Statistical
• Neuropsychological Tests
• Peptide Fragments (blood)
• Predictive Value of Tests
• Prospective Studies
• Reference Values
• Risk Factors