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Tau acetylation at K280 is critical for propagation and an antibody targeting it prevents in vivo tau propagation
Author(s) -
Yoon SeungYong,
Song Halim,
Kim NaYoung,
Kim DongHou
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047374
Subject(s) - in vivo , neocortex , tau protein , acetylation , in vitro , amyloid (mycology) , chemistry , antibody , hippocampus , biophysics , microbiology and biotechnology , biology , neuroscience , alzheimer's disease , biochemistry , immunology , pathology , medicine , disease , genetics , inorganic chemistry , gene
Abstract Background The spread of tau pathology from the transentorhinal cortex to the hippocampus and neocortex in Alzheimer’s disease (AD) is explained by the prion‐like cell‐to‐cell seeding and propagation of misfolded tau aggregates. Hence, it is important to define the seeding‐ and propagation‐competent tau species and to develop targeted therapeutic antibodies. Method Various methods like thioflavin‐T, FRET, FACS, and in vivo stereotaxic injection of AD‐derived tau aggregate fractions were used to evaluate tau aggregation, propagation, and the efficacy of an antibody to inhibit these processes. Result Acetylation of tau at K280 is critical for the successive tau propagation processes, including secretion, aggregation, and seeding. An antibody targeting acetylated tau at K280 effectively prevented AD‐derived insoluble tau aggregates‐induced proteopathic seeding and propagation in in vitro assays and in vivo mouse brains. Conclusion Acetylated tau at K280 is a core species of seeding and propagation, which could be a therapeutic target for AD and other tauopathies.