The relationship of plasma Aβ levels to dementia in aging individuals with mild cognitive impairment

Abstract

Amyloid β(Aβ) peptides are important components of plaques in Alzheimer's disease(AD). A decrease in the CSF concentration of Aβ40 and Aβ42 is a potential biomarker for incident AD. In contrast, studies on plasma Aβ40 and Aβ42 concentrations have yielded contradictory results. To explore the relationship between plasma Aβ40 and Aβ42 concentrations and AD in aging individuals with mild cognitive impairment (MCI), evaluate the sensitivity and the specificity of plasma Aβ and their ratio as a marker for progression to AD. We measured baseline concentrations of Aβ40 and Aβ42, and their ratio in plasma of patients carefully categorized clinically and neurochemically as having AD or other dementias from a cohort of patients with MCI (n=588) after 4-6 years of follow-up time. Plasma concentrations of Aβ40, Aβ42 were measured using a sandwich enzyme-linked immunosorbent assay technology. The association between plasma Aβ concentrations and the risk of dementia was assessed using Cox proportional hazard models. Optimal sensitivity and specificity of Aβ measurements were determined by ROC curve analysis. Plasma Aβ42 concentration and the Aβ42/Aβ40 ratio at baseline were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients. The baseline concentrations of Aβ40 were similar in all MCI groups. The Aβ42/Aβ40 ratio was superior to Aβ42 concentration with regard to identify incipient AD in MCI. The ratio of Aβ42 to Aβ40 rather than absolute levels of the peptides can aid in the identification of incipient AD among MCI patients. A potential role of plasma Aβ concentrations as a marker of incipient dementia warrants further investigation.