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Tau phosphosignatures discriminate Alzheimer Disease from other tauopathies
Author(s) -
Seyfried Nicholas,
Dammer Eric,
Ren Rujing,
Gearing Marla,
Duong Duc,
Lah James,
Levey Allan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb208
Subject(s) - tauopathy , progressive supranuclear palsy , corticobasal degeneration , phosphorylation , tau protein , frontotemporal dementia , neuroscience , threonine , chemistry , neurodegeneration , alzheimer's disease , disease , biochemistry , serine , biology , medicine , dementia
Neurofibrillary tangles (NFTs) comprised of highly phosphorylated tau are a core pathological feature of Alzheimer's disease (AD) and several other neurodegenerative diseases collectively termed tauopathies, which include progressive supranuclear palsy, corticobasal degeneration and certain frontotemporal dementias. There are six isoforms of human tau in brain and over 40 serine (S), threonine (T), and tyrosine (Y) tau phosphorylation sites have been identified. Phosphorylation of tau at specific S/T/Y sites is hypothesized to cause both functional deficits as well as gain‐of‐function toxicity that ultimately lead to NFT formation, synapse loss and cognitive dysfunction. Despite being clinically distinct diseases it remains unclear whether site‐specific tau phosphorylation differs between AD and other tauopathies. To address this question we employed immobilized metal affinity chromatography followed by liquid chromatography‐tandem mass spectrometry to identify and quantify tau phosphopeptides from individual AD, tauopathy and age‐matched control postmortem human brain tissues ( n = 7 per group). In total 77 tau phosphopeptides representing 32 S/T/Y sites were analyzed by weighted correlation network analysis to delineate tau phosphosites co‐enriched in a disease specific manner. Our findings suggest that the mechanisms underlying site‐specific tau phosphorylation differ between AD and other tauopathies.