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

Amyloid beta(A beta) peptides are important components of plaques in Alzheimer's disease(AD). A decrease in the CSF concentration of A beta 40 and A beta 42 is a potential biomarker for incident AD. In contrast, studies on plasma A beta 40 and A beta 42 concentrations have yielded contradictory results. To explore the relationship between plasma A beta 40 and A beta 42 concentrations and AD in aging individuals with mild cognitive impairment (MCI), evaluate the sensitivity and the specificity of plasma A beta and their ratio as a marker for progression to AD. We measured baseline concentrations of A beta 40 and A beta 42, 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 A beta 40, A beta 42 were measured using a sandwich enzyme-linked immunosorbent assay technology. The association between plasma A beta concentrations and the risk of dementia was assessed using cox proportional hazard models. Optimal sensitivity and specificity of A beta measurements were determined by ROC curve analysis. Plasma A beta 42 concentration and the A beta 42/A beta 40 ratio at baseline were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients. The baseline concentrations of A beta 40 were similar in all MCI groups. The A beta 42/A beta 40 ratio was superior to A beta 42 concentration with regard to identify incipient AD in MCI. The ratio of A beta 42 to A beta 40 rather than absolute levels of the peptides can aid in the identification of incipient AD among MCI patients. A potential role of plasma A beta concentrations as a marker of incipient dementia warrants further investigation. (C) 2011 Elsevier B.V. All rights reserved.