Association of plasma amyloid beta with risk of dementia: the prospective Three-City Study.
OBJECTIVE
Several lines of evidence indicate that a decrease in the CSF concentration of amyloid beta(42) (Abeta(42)) is a potential biomarker for incident Alzheimer disease. In contrast, studies on plasma Abeta(1-40) and Abeta(1-42) peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma Abeta(1-40) and Abeta(1-42) peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated Abeta (Abeta(n-40) and Abeta(n-42)) and the risk of dementia.


METHODS
During a subsequent 4-year follow-up period, 257 individuals presented incident dementia from 8,414 participants, and a subcohort of 1,185 individuals without dementia was drawn as a control cohort. Plasma levels of Abeta(1-40), Abeta(1-42), Abeta(n-40), and Abeta(n-42) were measured using an xMAP-based assay technology. The association between plasma Abeta peptide levels and the risk of dementia was assessed using Cox proportional hazard models.


RESULTS
Of the various Abeta variables analyzed, the Abeta(1-42)/Abeta(1-40) and Abeta(n-42)/Abeta(n-40) ratios presented the strongest association with the risk of dementia: people with a high Abeta(1-42)/Abeta(1-40) or Abeta(n-42)/Abeta(n-40) ratio had a lower risk of developing dementia. These associations were restricted to individuals diagnosed at 2 years of follow-up and the Abeta(n-42)/Abeta(n-40) ratio was mainly associated with the risk of mixed/vascular dementia.


CONCLUSIONS
Plasma Abeta peptide concentrations and Abeta(1-42)/Abeta(1-40) and Abeta(n-42)/Abeta(n-40) ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia.
Lambert
J-C
JC
Unité INSERM 744, Institut Pasteur de Lille, BP 245, 1, rue du professeur Calmette, F-59019 Lille cédex, France. jean-charles.lambert@pasteur-lille.fr
Schraen-Maschke
S
S
Richard
F
F
Fievet
N
N
Rouaud
O
O
Berr
C
C
Dartigues
J-F
JF
Tzourio
C
C
Alpérovitch
A
A
Buée
L
L
Amouyel
P
P
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000097:blood*; D003704:Dementia / Q000097:blood* / Q000175:diagnosis; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011933:Reagent Kits, Diagnostic; C075222:amyloid beta-protein (1-42)