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Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent‐insoluble paired helical filament tau binding protein
Author(s) -
Wang Qin,
Woltjer Randall L.,
Cimino P. J.,
Pan Catherine,
Montine Kathleen S.,
Zhang Jing,
Montine Thomas J.
Publication year - 2005
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/fj.04-3210fje
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , chemistry , tau protein , alzheimer's disease , neurofibrillary tangle , laser capture microdissection , hippocampal formation , proteomics , microbiology and biotechnology , biochemistry , pathology , neuroscience , biology , enzyme , medicine , senile plaques , disease , dehydrogenase , gene expression , gene
We performed proteomic analysis of neurofibrillary tangles (NFTs) obtained by laser capture microdissection from pyramidal neurons in hippocampal sector CA1 in patients with Alzheimer disease (AD) using liquid chromatography (LC)‐mass spectrometry (MS)/MS. We discovered a total of 155 proteins in laser captured NFT's, 72 of which were identified by multiple unique peptides. Of these 72 proteins, 63 had previously unknown association with NFTs; one of these was glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). We validated by immunohistochemistry that GAPDH colocalized with the majority of NFTs as well as plaque‐like structures in AD brain and was co‐immunoprecipitated by antibodies to abnormal forms of tau in AD, but not tau from AD temporal cortex. Characterization of GAPDH showed that it, along with phosphorylated tau and Aβ peptides, was present in detergent‐insoluble fractions from AD temporal cortex but not from age‐matched controls. These data are the first proteomic investigation of NFTs. Moreover, our results validate this approach by demonstrating that GAPDH, a glycolytic and microtubule binding protein, not only co‐localized to NFTs and immunoprecipitated with PHF‐tau, but also is one of the few proteins known to undergo conversion to a detergent‐insoluble form in AD.