Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau.
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.
Matsuo
E S
ES
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
Shin
R W
RW
Billingsley
M L
ML
Van deVoorde
A
A
O'Connor
M
M
Trojanowski
J Q
JQ
Lee
V M
VM
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*
D016875:tau Proteins; D010749:Phosphoprotein Phosphatases