Biochemical characterization of Abeta 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 (PHF_{tau}) 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, PHF_{tau} and insoluble Abeta_{42} 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 PHF_{tau}) 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.
Tremblay
Cyntia
C
Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l'Université Laval (CHUL) Research Center, Quebec (QC), Canada.
Pilote
Mireille
M
Phivilay
Alix
A
Emond
Vincent
V
Bennett
David A
DA
Calon
Frédéric
F
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D015415:Biomarkers; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins