Elevation of the Plasma Aβ 40 /Aβ 42 Ratio as a Diagnostic Marker of Sporadic Early-Onset Alzheimer’s Disease

Abstract

Background: Although plasma amyloid-β (Aβ) 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 Aβ 40 , Aβ 42 , and the Aβ 40 /Aβ 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 Aβ 40 and Aβ 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 Aβ 42 were significantly lower, while the Aβ 40 /Aβ 42 ratio was significantly higher in sEOAD patients than in controls. The levels of Aβ 40 , Aβ 42 , and the Aβ 40 /Aβ 42 ratio did not differ in relation to the APOE ɛ 4 allele. The CSF/plasma albumin ratio was comparable between the two groups, and the plasma parameters of Aβ proteins were not significantly associated. A multivariate analysis revealed that an increased Aβ 40 /Aβ 42 ratio is valuable for the discrimination of sEOAD from controls (β= 0.344, p = 0.000). The area under the ROC curve for the Aβ 40 /Aβ 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 Aβ 40 /Aβ 42 ratio had moderate validity for the discrimination of sEOAD patients from age-matched controls.