Plasma A 42 and A 40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study

Abstract

BackgroundSingle measurements of plasma Aβ are not useful in the diagnostics of Alzheimer's disease (AD). However, changes in plasma Aβ levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment.ObjectiveTo examine the relation of baseline and serial plasma Aβ levels to cognitive change in follow-up.Methods269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aβ levels were measured using ELISA.ResultsSubjects who declined cognitively during the follow-up had lower levels of plasma Aβ42 at the baseline. Plasma Aβ42 and the Aβ42/Aβ40 ratio decreased (−2.4 pg/ml for Aβ42 in 6 years) in those who declined in follow-up, whereas Aβ42 and the Aβ42/Aβ40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aβ40.ConclusionsLow or decreasing plasma Aβ42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aβ42 may be useful in the detection of the subjects who are at risk for cognitive decline.

Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer’s disease

“…Many candidate markers related to the AD pathophysiology have been tested with promising results, e.g., serum and/or plasma concentrations of the amyloid-beta peptide (Ab 42 ) (Seppälä et al 2010), neurotrophic (Forlenza et al 2010a) and inflammatory factors (Diniz et al 2010), and markers of oxidative stress (Pratico et al 2002). A recent study has concomitantly addressed serum concentrations of several markers of hypoxia, oxidative stress and membrane lipid remodeling with a metabolomics model (Oresic et al 2011).…”

Nutrient intake and plasma β-amyloid

“…Our outcome is not a stable trait but rather a moving target with temporal dynamic changes, because previous studies have consistently shown that blood A␤ levels change during the process of AD development. 7,9,12 A single assessment of A␤s may be susceptible to short-term variation. There could also be measurement error of nutrients from the SFFQ, which could bias our results if reporting error is associated with the A␤ measurements.…”

“…Although we used caloric intake-adjusted residuals for nutrient variables, we also included caloric intake as a covariate in the models. 25 Finally, in a fully adjusted model, we additionally adjusted for alcohol drinking, use of medication (medications affecting blood vessel thrombus formation propensity including warfarin, heparin, aspirin, and antiplatelet and antidiabetic agents including insulin and oral hypoglycemic), 12,27 and intake of nutrients from supplements (except for MUFA and SFA, for which no supplements were consumed). For nutrients that appeared to be associated with A␤ levels, we further examined their food sources by examining the correlations between foods and the nutrients.…”

“…6 Several large-scale studies have found that plasma levels of A␤ peptides have predictive value for AD or cognitive decline. [7][8][9][10][11][12] In the present study, we aimed to examine whether dietary intake of nutrients was associated with plasma A␤ levels in a cross-sectional analysis of an elderly (65 years or older) New York population.…”

Genetic risk factor APOEε4 associates with plasma amyloid beta in amnestic mild cognitive impairment and alzheimer’s disease

“…42 Low plasma Aβ 42 at baseline was associated with cognitive decline occurring during follow up. 43 We found no statistical significance of differences in plasma Aβ 42 levels and Aβ 42 /Aβ 40 ratio among AD, MCI, and HC groups, but there is a tendency that both are lower in aMCI and AD subjects than in HC subjects. Interestingly, plasma Aβ 40 is much higher in AD subjects compared to HC and aMCI subjects.…”