Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau

Eriko S. Matsuo, Ryong Woon Shin, Melvin L. Billingsley, Andre Van deVoorde, Michael O'Connor, John Q. Trojanowski, Virginia M.Y. Lee

Research output: Contribution to journalArticlepeer-review

518 Scopus citations

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 213 (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.

Original languageEnglish (US)
Pages (from-to)989-1002
Number of pages14
JournalNeuron
Volume13
Issue number4
DOIs
StatePublished - Oct 1994

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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