Dephosphorylation Passivates the Seeding Activity of Oligomeric Tau Derived From Alzheimer’s Brain

• Published in: Frontiers in molecular neuroscience Vol. 14; p. 631833
• Main Authors: Wu, Ruozhen, Li, Longfei, Shi, Ruirui, Zhou, Yan, Jin, Nana, Gu, Jianlan, Tung, Yunn Chyn, Liu, Fei, Chu, Dandan
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 13-05-2021; Frontiers Media S.A
• Subjects: Alkaline phosphatase; Alzheimer's disease; Brain research; Dephosphorylation; Epitopes; Fluorides; Neurodegenerative diseases; Neurofibrillary tangles; Neuroscience; oligomerictau derived from AD brain; Pathology; Phosphatase; Phosphorylation; Propagation; Proteins; seedingactivity; Seeds; Tau protein; Western blotting; United States > US
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2021.631833

Accumulation of intracellular neurofibrillary tangles (NFTs), which are constituted of abnormally phosphorylated tau, is one of the neuropathological hallmarks of Alzheimer’s disease (AD). The oligomeric aggregates of tau in AD brain (AD O-tau) are believed to trigger NFT spreading by seeding normal tau aggregation as toxic seeds, in a prion-like fashion. Here, we revealed the features of AD O-tau by Western blots using antibodies against various epitopes and determined the effect of dephosphorylation on the seeding activity of AD O-tau by capture and seeded aggregation assays. We found that N-terminal truncated and C-terminalhyperphosphorylated tau species were enriched in AD O-tau. Dephosphorylation of AD O-tau by alkaline phosphatasediminished its activity in capturing tau
in vitro
and ininducing insoluble aggregates in cultured cells. Our resultssuggested that dephosphorylation passivated the seeding activity ofAD O-tau. Inhibition of phosphorylation may be a potentstrategy to prevent the spreading of tau patho3logy.