Acetylated tau neuropathology in sporadic and hereditary 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

Research output: Contribution to journalArticle

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Abstract

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.

LanguageEnglish (US)
Pages344-351
Number of pages8
JournalAmerican Journal of Pathology
Volume183
Issue number2
DOIs
StatePublished - Aug 1 2013

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Tauopathies
Frontotemporal Dementia
Flavin-Adenine Dinucleotide
Pick Disease of the Brain
Amyloid
Neuroglia
Alzheimer Disease
Neuropil Threads
Progressive Supranuclear Palsy
Chromosomes, Human, Pair 17
Neurofibrillary Tangles
Acetylation
Lysine
Biomarkers
Neuropathology
Antibodies
Brain
thioflavin T

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., McCarty-Wood, E., Van Deerlin, V. M., ... Trojanowski, J. Q. (2013). Acetylated tau neuropathology in sporadic and hereditary tauopathies. American Journal of Pathology, 183(2), 344-351. DOI: 10.1016/j.ajpath.2013.04.025

Acetylated tau neuropathology in sporadic and hereditary tauopathies. / Irwin, David J.; Cohen, Todd J.; Grossman, Murray; Arnold, Steven E.; McCarty-Wood, Elisabeth; Van Deerlin, Vivianna M.; Lee, Virginia M.Y.; Trojanowski, John Q.

In: American Journal of Pathology, Vol. 183, No. 2, 01.08.2013, p. 344-351.

Research output: Contribution to journalArticle

Irwin, DJ, Cohen, TJ, Grossman, M, Arnold, SE, McCarty-Wood, E, Van Deerlin, VM, Lee, VMY & Trojanowski, JQ 2013, 'Acetylated tau neuropathology in sporadic and hereditary tauopathies' American Journal of Pathology, vol. 183, no. 2, pp. 344-351. DOI: 10.1016/j.ajpath.2013.04.025
Irwin DJ, Cohen TJ, Grossman M, Arnold SE, McCarty-Wood E, Van Deerlin VM et al. Acetylated tau neuropathology in sporadic and hereditary tauopathies. American Journal of Pathology. 2013 Aug 1;183(2):344-351. Available from, DOI: 10.1016/j.ajpath.2013.04.025
Irwin, David J. ; Cohen, Todd J. ; Grossman, Murray ; Arnold, Steven E. ; McCarty-Wood, Elisabeth ; Van Deerlin, Vivianna M. ; Lee, Virginia M.Y. ; Trojanowski, John Q./ Acetylated tau neuropathology in sporadic and hereditary tauopathies. In: American Journal of Pathology. 2013 ; Vol. 183, No. 2. pp. 344-351
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