Elevation of the plasma Aβ40/Aβ42 ratio as a diagnostic marker of sporadic early-onset Alzheimer's disease

Hyeong Jun Kim, Kyung Won Park, Tae Eun Kim, Ji Young Im, Ho Sik Shin, Saeromi Kim, Dong Hyun Lee, Byoung Seok Ye, Jong Hun Kim, Eun Joo Kim, Kee Hyung Park, Hyun Jeong Han, Jee Hyang Jeong, Seong Hye Choi, Sun Ah Park

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 β4 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.

Original languageEnglish
Pages (from-to)1043-1050
Number of pages8
JournalJournal of Alzheimer's Disease
Volume48
Issue number4
DOIs
StatePublished - 27 Oct 2015

Keywords

  • Alzheimer's disease
  • amyloid-β protein
  • biomarker
  • blood-brain barrier
  • plasma

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