New Assay for Old Markers-Plasma Beta Amyloid of Mild Cognitive Impairment and Alzheimer's Disease

Although there is a consensus on the reduced levels of A beta 1-42 in the CSF of patients with AD, studies of plasma A beta levels were inconsistent and have limited clinical value. We developed an immunomagnetic reduction assay (IMR) to determine the plasma levels of A beta. We surveyed patients with varying AD severity (CDR = 0.5, n= 16; CDR >= 1, n= 18) and controls (n= 26). Significant group differences were apparent in the levels of A beta 1-42 (F = 5.54, p = 0.002) and the A beta 1-42/A beta 1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed significant differences in the A beta 1-42 levels of controls and AD patients (p = 0.001) and in the A beta 1-42/A beta 1-40 ratio of control, MCI and AD subjects (all p <= 0.001). Regression analysis of A beta 1-42/A beta 1-40 ratios on dementia severity showed an adjusted R-2 of 0.553 (p = 0.001). We identified a cut-off of 16.1 pg/ml for A beta 1-42 to differentiate control subjects from patients (both AD and MCI) with 85.3% sensitivity and 88.5% specificity. We also obtained a cut-off value of 0.303 for A beta 1-42/A beta 1-40 ratios with 85.3% sensitivity and 96.2% specificity. APOE epsilon 4 carriers had significantly higher A beta 1-42/A beta 1-40 ratios than the non-carriers (F = 4.839, p = 0.015). An independent group of case-control subjects validated both cut-off values for A beta 1-42/A beta 1-40 (100% sensitivity and 83.3% specificity) and for A beta 1-42 (100% sensitivity and 75.3% specificity). In a subgroup of longitudinal follow-up study, we found that the plasma A beta was relatively stable with an interval of approximately 3 months. In conclusion, we found that the plasma A beta 1-42 is a useful biomarker for AD. The A beta 1-42/A beta 1-40 ratio improves the diagnostic power of the plasma A beta biomarkers. The iron nanoparticles and IMR provides a novel method to measure plasma A beta and could serve as an important clinical tool for the diagnosis of neurodegenerative diseases.