Document Detail

Acetylated tau neuropathology in sporadic and hereditary tauopathies.
MedLine Citation:
PMID:  23885714     Owner:  NLM     Status:  MEDLINE    
We have recently shown acetylation of tau at lysine residue 280 (AC-K280) to be a disease-specific modification in Alzheimer disease (AD), corticobasal degeneration, and progressive supranuclear palsy, likely representing a major regulatory tau modification. Herein, we extend our observations using IHC with a polyclonal antibody specific for AC-K280. Thirty brain regions were examined in argyrophilic grain disease (AGD; n = 5), tangle-predominant senile dementia (TPSD; n = 5), Pick disease (n = 4), familial AD (FAD; n = 2; PSEN1 p.G206A and p.S170P), and frontotemporal dementia with parkinsonism linked to chromosome-17 (FTDP-17; n = 2; MAPT p.P301L and IVS10 + 16). All AGD, TPSD, FAD, and FTDP-17 cases had significant AC-K280 reactivity that was similar in severity and distribution to phosphorylated tau. AC-K280 robustly labeled grain pathological characteristics in AGD and was predominantly associated with thioflavin-S-positive neurofibrillary tangles and less reactive in neuropil threads and extracellular tangles in TPSD and FAD. Thioflavin-S-negative neuronal and glial inclusions of patients with FTDP-17 were robustly AC-K280 reactive. A low degree of AC-K280 was found in a subset of 4-repeat tau-containing lesions in Pick disease. AC-K280 is a prominent feature of both neuronal and glial tau aggregations in tauopathies of various etiologies. The close association of AC-K280 with amyloid and pre-amyloid conformations of tau suggests a potential role in tangle maturation and, thus, could serve as a useful biomarker or therapeutic target in a variety of tauopathies.
David J Irwin; Todd J Cohen; Murray Grossman; Steven E Arnold; Elisabeth McCarty-Wood; Vivianna M Van Deerlin; Virginia M-Y Lee; John Q Trojanowski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The American journal of pathology     Volume:  183     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-07-26     Completed Date:  2013-10-24     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  344-51     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Biological Markers / metabolism
Brain / metabolism*
Lysine / metabolism*
Tauopathies / diagnosis*,  genetics,  metabolism
tau Proteins / metabolism*
Grant Support
AG17586/AG/NIA NIH HHS; P01 AG017586/AG/NIA NIH HHS; P30 AG010124/AG/NIA NIH HHS; P30 AG10124/AG/NIA NIH HHS; T32 AG000255/AG/NIA NIH HHS; T32-AG000255/AG/NIA NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/tau Proteins; K3Z4F929H6/Lysine

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