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.
