Elevation of the Plasma Aβ40/Aβ42 Ratio as a Diagnostic Marker of Sporadic Early-Onset Alzheimer’s Disease

• Published in: Journal of Alzheimer's disease 2015-10, Vol.48 (4), p.1043-1050
• Main Authors: Kim, Hyeong Jun, Park, Kyung Won, Kim, Tae Eun, Im, Ji Young, Shin, Ho Sik, Kim, Saeromi, Lee, Dong Hyun, Ye, Byoung Seok, Kim, Jong Hun, Kim, Eun-Joo, Park, Kee Hyung, Han, Hyun Jeong, Jeong, Jee Hyang, Choi, Seong Hye, Park, Sun Ah
• Format: Article
• Language: English
• Subjects: Age of Onset; Aged; Albumins - cerebrospinal fluid; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Amyloid beta-Peptides - blood; Apolipoprotein E4 - genetics; Area Under Curve; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Blood-Brain Barrier - metabolism; Capillary Permeability; Female; Humans; Male; Middle Aged; Multivariate Analysis; Peptide Fragments - blood; ROC Curve; Sensitivity and Specificity; Serum Albumin - metabolism
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-143018

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 Aβ40, Aβ42, and the Aβ40/Aβ42 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 Aβ40 and Aβ42 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 Aβ42 were significantly lower, while the Aβ40/Aβ42 ratio was significantly higher in sEOAD patients than in controls. The levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio did not differ in relation to the APOE ɛ4 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 Aβ40/Aβ42 ratio is valuable for the discrimination of sEOAD from controls (β= 0.344, p = 0.000). The area under the ROC curve for the Aβ40/Aβ42 ratio was 0.76, and a cut-off ratio of 5.87 was suggested to have 70% sensitivity and 68% specificity. Conclusion: The plasma Aβ40/Aβ42 ratio had moderate validity for the discrimination of sEOAD patients from age-matched controls.