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

Article type: Research Article

Authors: Kim, Hyeong Jun^{a; 1} | Park, Kyung Won^{b; 1} | Kim, Tae Eun^a | Im, Ji Young^a | Shin, Ho Sik^a | Kim, Saeromi^a | Lee, Dong Hyun^a | Ye, Byoung Seok^c | Kim, Jong Hun^d | Kim, Eun-Joo^e | Park, Kee Hyung^f | Han, Hyun Jeong^g | Jeong, Jee Hyang^h | Choi, Seong Hyeⁱ | Park, Sun Ah^{a; *}

Affiliations: [a] Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea | [b] Department of Neurology, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Korea | [c] Department of Neurology, Yonsei University College of Medicine, Seoul, Korea | [d] Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, Goyang, Korea | [e] Department of Neurology, Pusan National University Hospital, Busan, Korea | [f] Department of Neurology, Gachon University, College of Medicine, Incheon, Korea | [g] Department of Neurology, Myongii Hospital, Seonam University College of Medicine, Goyang, Korea | [h] Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, Korea | [i] Department of Neurology, Inha University School of Medicine, Incheon, Korea

Correspondence: [*] Correspondence to: Sun Ah Park, MD, PhD, Departments of Neurology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon, Republic of Korea, 420-767. Tel.: +82 32 621 5221; Fax: +82 32 621 5014; E-mail: [email protected]

Note: [] These two authors contributed equally to this work.

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.

Keywords: Alzheimer’s disease, amyloid-β protein, biomarker, blood-brain barrier, plasma

DOI: 10.3233/JAD-143018

Journal: Journal of Alzheimer's Disease, vol. 48, no. 4, pp. 1043-1050, 2015