title: Acetylated tau neuropathology in sporadic and hereditary tauopathies.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Cohen
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Elisabeth
authors.initials: E
authors.lastname: McCarty-Wood
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000107:Acetylation; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000378:metabolism*; D024801:Tauopathies / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016875:tau Proteins; D008239:Lysine