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P2‐171: THE POLY(A) BINDING PROTEIN MSUT2 MODULATES GLIOSIS IN TAUOPATHY
Author(s) -
Kraemer Brian C.,
McMillan Pamela,
Strovas Timothy C.,
Keene Dirk,
Schellenberg Gerard D.,
Wheeler Jeanna M.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.858
Subject(s) - tauopathy , neurodegeneration , biology , transgene , tau protein , caenorhabditis elegans , genetically modified mouse , neuroscience , gene knockout , alzheimer's disease , microbiology and biotechnology , genetics , gene , disease , pathology , medicine
also examined in other tauopathies (FTLD-Tau and corticobasal degeneration), other rare amyloidoses (familial Danish dementia, HCHWA-D, Hungarian amyloidosis), and in Down syndrome. Interaction of secernin-1 with phosphorylated tau or Ab in human cortical tissue was examined using co-immunoprecipitation. Results: Immunohistochemistry showed that secernin-1 is a neuronal protein that abundantly accumulates in NFTs and plaque-associated dystrophic neurites in AD. Quantification of secernin-1 immunohistochemistry confirmed that there was significantly more secernin-1 inside NFTs in comparison to surrounding neurons (p<0.0001). Secernin-1 colocalization in NFTs appeared early in NFT development; secernin-1 was present in NFTs in MCI and secernin-1 colocalized with the antibodyMC1, a marker of early NFT development. Additionally, there was increased secernin-1 expression in Down syndrome. Unexpectedly, secernin-1 did not colocalize with phosphorylated tau positive lesions in other types of tauopathies, suggesting that its presence is specific to NFTs in AD. Co-immunoprecipitation studies showed that secernin-1 directly bound to phosphorylated tau in human AD brains. Further co-immunoprecipitation studies are ongoing to determine whether secernin-1 also binds to Ab. Conclusions:Here we present evidence that secernin-1 is a novel early marker of NFTs in AD. Protein binding studies suggest that its presence in NFTs is a result of direct binding to phosphorylated tau. As such, secernin-1 has potential as a novel therapeutic target for AD and could serve as a useful biomarker for AD.