Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study.
OBJECTIVE
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.
Lopez
O L
OL
Department of Psychiatry and Neurology, University of Pittsburgh, PA, USA. lopezol@upmc.edu
Kuller
L H
LH
Mehta
P D
PD
Becker
J T
JT
Gach
H M
HM
Sweet
R A
RA
Chang
Y F
YF
Tracy
R
R
DeKosky
S T
ST
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000453:epidemiology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D015233:Models, Statistical; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)