title: Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau.
abstract: Tau from Alzheimer's disease (AD) paired helical filaments (PHF-tau) is phosphorylated at sites not found in autopsy-derived adult tau from normal human brains, and this suggested that PHF-tau is abnormally phosphorylated. To explore this hypothesis, we examined human adult tau from brain biopsies and demonstrated that biopsy-derived tau is phosphorylated at most sites thought to be abnormally phosphorylated in PHF-tau. These sites also were phosphorylated in autopsy-derived human fetal tau and rapidly processed rat tau. The hypophosphorylation of autopsy-derived adult human tau is due to rapid dephosphorylation postmortem, and protein phosphatases 2A (PP2A) and 2B (PP2B) in human brain biopsies dephosphorylate tau in a site-specific manner. The down-regulation of phosphatases (i.e., PP2A and PP2B) in the AD brain could lead to the generation of maximally phosphorylated PHF-tau that does not bind microtubules and aggregates as PHFs in neurofibrillary tangles and dystrophic neurites.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
authors.forename: E S
authors.initials: ES
authors.lastname: Matsuo
authors.forename: R W
authors.initials: RW
authors.lastname: Shin
authors.forename: M L
authors.initials: ML
authors.lastname: Billingsley
authors.forename: A
authors.initials: A
authors.lastname: Van deVoorde
authors.forename: M
authors.initials: M
authors.lastname: O'Connor
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011180:Postmortem Changes; D017433:Protein Structure, Secondary; D051381:Rats; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D010749:Phosphoprotein Phosphatases