Characterization of two pathological tau protein, variants in Alzheimer brain cortices.
Tau proteins were detected in brain tissue homogenates from 10 patients with Alzheimer's disease versus 10 age-matched controls using the immunoblot technique and 2 polyclonal antibodies: anti-paired helical filaments (PHF) and anti-human native Tau proteins. In control brains, both antisera detected identically the normal set of Tau proteins, with molecular weight (MW) ranging from 45 to 62 kDa. Moreover, in association areas of neocortex from Alzheimer brains, the antisera detected 2 additional Tau variants of 64 and 69 kDa. Tau 64 and 69 were not found in regions of Alzheimer brains where the Alzheimer pathology was absent (caudate nucleus or cerebellum for example). The heavy MW of Tau 64 and 69 is due to their phosphorylation state as shown by the decrease of their MW after alkaline phosphatase treatment. Therefore, Tau 64 and Tau 69 are specific markers of the Alzheimer's disease neuronal degenerating process and their characterization demonstrates that an abnormal phosphorylation of Tau really occurs during the disease. Tau 64 and 69 were isolated with normal Tau proteins while the PHF were insoluble. Therefore, Tau proteins are likely to be abnormally phosphorylated prior to their incorporation in the PHF structure. Consequently, they might appear before the lesions and might be instrumental for the search of biochemical deregulations that precede the neurofibrillary degeneration.
Flament
S
S
INSERM U.16, Laboratoire de Neurosciences, ADERMA, Faculté de Médecine, Lille, France.
Delacourte
A
A
Hémon
B
B
Défossez
A
A
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009454:Neurofibrils / Q000473:pathology*; D010766:Phosphorylation; D016875:tau Proteins
D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D000469:Alkaline Phosphatase