Elevation of the Plasma A beta(40)/A beta(42) Ratio as a Diagnostic Marker of Sporadic Early-Onset Alzheimer's Disease

Abstract

Background: Although plasma amyloid-beta (A beta) levels have been evaluated as a possible diagnostic marker of Alzheimer's disease (AD), the findings are inconsistent. Objective: The present study aimed to validate plasma levels of A beta(40), A beta(42), and the A beta(40)/A beta(42) ratio as biomarkers of AD in subjects with early-onset AD (EOAD) without familial AD genetic mutations. Methods: Patients with sporadic EOAD (sEOAD) were prospectively recruited by nine neurology clinics. Plasma levels of A beta(40) and A beta(42) were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in 100 sEOAD (50-69 year-old) and 46 age-matched normal control subjects (50-72 year-old). Cerebrospinal fluid (CSF) was obtained from 32 sEOAD subjects and 25 controls. The integrity of the blood-brain barrier was assessed using the CSF/plasma albumin ratio. Results: The plasma levels of A beta(42) were significantly lower, while the A beta(40)/A beta(42) ratio was significantly higher in sEOAD patients than in controls. The levels of A beta(40), A beta(42), and the A beta(40)/A beta(42) ratio did not differ in relation to the APOE epsilon 4 allele. The CSF/plasma albumin ratio was comparable between the two groups, and the plasma parameters of A beta proteins were not significantly associated. A multivariate analysis revealed that an increased A beta(40)/A beta(42) ratio is valuable for the discrimination of sEOAD from controls (beta = 0.344, p = 0.000). The area under the ROC curve for the A beta(40)/A beta(42) ratio was 0.76, and a cut-off ratio of 5.87 was suggested to have 70% sensitivity and 68% specificity. Conclusion: The plasma A beta(40)/A beta(42) ratio had moderate validity for the discrimination of sEOAD patients from age-matched controls.