Biochemical Characterization of Aβ and Tau Pathologies in Mild Cognitive Impairment and Alzheimer's Disease

We report a post mortem biochemical analysis of amyloid-beta (Abeta) (ELISA) and tau (Western immunoblots) in the temporo-parietal neocortex of subjects with a clinical diagnosis of mild cognitive impairment (MCI, n=12), Alzheimer's disease (AD, n=12) or no cognitive impairment (NCI, n=12). Levels of Abeta ₄₂ in the detergent-insoluble protein fractions were significantly higher in persons with AD but did not differentiate individuals with MCI. Conversion of tau into its insoluble form (soluble/insoluble tau ratio) or into paired helical filament tau (PHFₜₐᵤ) were the biochemical variables most closely related to clinical and neuropathological diagnoses, but they did not distinguished MCI from the two other groups. Interestingly, soluble/insoluble total tau ratio, PHFₜₐᵤ and insoluble Abeta₄₂ concentrations in the cortex correlated strongly with global cognition scores proximate to death and with immunohistochemical and histological quantification of Abeta and tau pathologies. Our data suggest that 1) insoluble Abeta ₄₂ and insoluble tau (total or PHFₜₐᵤ) show a significant relationship with the clinical and neuropathological diagnosis of AD; 2) Although MCI appears to represent an intermediate stage between NCI and AD, the quantification of cortical Abeta and tau pathologies did not significantly distinguish subjects with MCI from either group.