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Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation.

TitleArgyrophilic grain disease differs from other tauopathies by lacking tau acetylation.
Publication TypeJournal Article
Year of Publication2013
AuthorsGrinberg LTenenholz, Wang X, Wang C, Sohn PDongmin, Theofilas P, Sidhu M, Arevalo JBenjamin, Heinsen H, Huang EJ, Rosen H, Miller BL, Gan L, Seeley WW
JournalActa Neuropathol
Volume125
Issue4
Pagination581-93
Date Published2013 Apr
ISSN1432-0533
KeywordsAcetylation, Aged, Aged, 80 and over, Brain, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neurofibrillary Tangles, Phosphorylation, Plaque, Amyloid, Protein Processing, Post-Translational, tau Proteins, Tauopathies
Abstract

Post-translational modifications play a key role in tau protein aggregation and related neurodegeneration. Because hyperphosphorylation alone does not necessarily cause tau aggregation, other post-translational modifications have been recently explored. Tau acetylation promotes aggregation and inhibits tau's ability to stabilize microtubules. Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both 3R and 4R tau, and used immunohistochemistry and immunofluorescence to probe 22 cases, including AD and another eight familial or sporadic tauopathies. Acetylated tau was identified in all tauopathies except argyrophilic grain disease (AGD). AGD is an age-associated, common but atypical 4R tauopathy, not always associated with clinical progression. Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies. The lack of acetylated tau in these inclusions suggests that AGD represents a distinctive tauopathy. Our data converge with previous findings to raise the hypothesis that AGD could play a protective role against the spread of AD-related tau pathology. Tau acetylation as a key modification for the propagation tau toxicity deserves further investigation.

DOI10.1007/s00401-013-1080-2
Alternate JournalActa Neuropathol.
PubMed ID23371364
PubMed Central IDPMC3692283
Grant ListP50 AG023501 / AG / NIA NIH HHS / United States
R01AG040311 / AG / NIA NIH HHS / United States
R01 AG036884 / AG / NIA NIH HHS / United States
R01 AG040311 / AG / NIA NIH HHS / United States
R01AG030207 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
R01 AG030207 / AG / NIA NIH HHS / United States
R01 AG033017 / AG / NIA NIH HHS / United States