Affiliations: [a] Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l'Université Laval (CHUL) Research Center, Quebec (QC), Canada | [b] Faculty of Pharmacy, Laval University, Quebec (QC), Canada | [c] Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
Correspondence:
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Correspondence: Dr. Frédéric Calon, Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l'Université Laval (CHUL) Research Center, 2705 Laurier Blvd, Quebec, QC, Canada, G1V 4G2. Tel.: +1 418 654 2296; Fax: +1 418 654 2761; E-mail: [email protected].
Note: [] Communicated by Alexandre Valério de Mendonça
Abstract: We report a post mortem biochemical analysis of amyloid-β (Aβ) (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 Aβ42 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 Aβ42 concentrations in the cortex correlated strongly with global cognition scores proximate to death and with immunohistochemical and histological quantification of Aβ and tau pathologies. Our data suggest that 1) insoluble Aβ42 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 Aβ and tau pathologies did not significantly distinguish subjects with MCI from either group.
