Plasma concentrations of free amyloid β cannot predict the development of Alzheimer's disease

Abstract

Introduction: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid β (Aβ)-central in the pathogenesis of AD-is a logical candidate, but studies to date have produced conflicting results on its utility.

Methods: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNO-BIA plasma Aβ form assays to determine concentrations of free plasma Aβ₄₀ and Aβ₄₂.

Results: Plasma concentrations of free Aβ₄₀ and Aβ₄₂ did not differ between preclinical AD cases and dementia-free controls, in the full sample or in subgroups defined according to sex and age group (<60 and ≥ 60 years). The interval between sampling and AD diagnosis did not affect the results. Aβ concentrations did not change in the years preceding AD diagnosis among individuals for whom longitudinal samples were available.

Discussion: Plasma concentrations of free Aβ could not predict the development of clinical AD, and Aβ concentrations did not change in the years preceding AD diagnosis in this sample. These results indicate that free plasma Aβ is not a useful biomarker for the identification of individuals at risk of developing clinical AD.

Keywords: Alzheimer's disease; Aβ; Biomarker; Dementia; Plasma amyloid β; Preclinical Alzheimer's disease.