Several Direct and Calculated Biomarkers from the Amyloid-β Pool in Blood are Associated with an Increased Likelihood of Suffering from Mild Cognitive Impairment

Validation of cost-effective, non-invasive methods to identify early (pre-clinical) Alzheimer's disease (AD) is increas- ingly becoming a key research challenge. We have developed two ELISA sandwich colorimetric tests for the accurate detection of amyloid- (A)1-40 and A1-42: i) directly accessible (DA) in the plasma, ii) recovered from the plasma sample (RP) after diluting the plasma sample in a formulated buffer, and iii) associated with the remaining cellular pellet (CP). These tests were carried out on samples from healthy controls (n = 19) and individuals with mild cognitive impairment (MCI; n = 27) with amnestic- hippocampal syndrome to investigate whether this comprehensive approach may help to explain the association between blood A levels and MCI. A logistic regression analysis detected seven direct or calculated markers (CP 40, DA 42, RP 42, DA/CP 40, DA/RP 42, DA/CP 42, and DA 42/40) with significant odds ratios (OR) after they were dichotomized with regard to the median of the pooled population. In particular, the likelihood (OR (95% CI)) of having MCI for patients with catCP 40, catDA/RP 42, catDA/CP 42, or catDA 42/40 below the corresponding population median ("positive test") was 11.48 (1.87-70.52), 22.09 (3.19-152.61), 11.48 (1.87-70.50), and 9.54 (1.77-51.38)-fold higher, respectively, than in those with a "negative test" after adjusting for the effect of the ApoE genotype. These results are congruent with the hypothesis that changes in blood A levels may be associated with the initial stages of AD. Thus, these A blood biomarkers might be useful tools for screening for those at increased risk of developing AD.