@article{9fafde643d3544cdbef446c5cfa56425,
title = "Tau Phosphorylation is Impacted by Rare AKAP9 Mutations Associated with Alzheimer Disease in African Americans",
abstract = "We studied the effect of two rare mutations (rs144662445 and rs149979685) in the A-kinase anchoring protein 9 (AKAP9) gene, previously associated with Alzheimer disease (AD) in African Americans (AA), on post-translational modifications of AD-related pathogenic molecules, amyloid precursor protein (APP) and microtubule-associated protein Tau using lymphoblastoid cell lines (LCLs) from 11 AA subjects with at least one AKAP9 mutation and 17 AA subjects lacking these mutations. LCLs were transduced by viral vectors expressing causative AD mutations in APP or human full-length wild type Tau. Cell lysates were analyzed for total APP, Aβ40, and total and T181 phospho-Tau (pTau). AKAP9 mutations had no effect on Aβ40/APP, but significantly increased pTau/Tau ratio in LCLs treated with phosphodiesterase-4 inhibitor rolipram, which activates protein kinase A. Proteomic analysis of Tau interactome revealed enrichment of RNA binding proteins and decrease of proteasomal molecules in rolipram-treated cells with AKAP9 mutations. This study shows the impact of rare functional AKAP9 mutations on Tau, a central mechanism of AD pathogenesis, in LCLs derived from AD and control subjects.",
keywords = "AKAP9, APP, African American, Alzheimer disease, Amyloid-β peptide, Rolipram, Tau",
author = "Tsuneya Ikezu and Cidi Chen and DeLeo, {Annina M.} and Ella Zeldich and Fallin, {M. Daniele} and Kanaan, {Nicholas M.} and Lunetta, {Kathryn L.} and Abraham, {Carmela R.} and Logue, {Mark W.} and Farrer, {Lindsay A.}",
note = "Funding Information: Acknowledgements This study was funded in-part by grants from the National Institute on Aging (NIA, R01-AG048927, U01-AG032984, P30-AG13846, and RF1-AG054199) and Alzheimer{\textquoteright}s Association (DVT-14320835 and AARF-16442664). Biological samples used in this study were prepared by the Molecular Genetics Core Facility at Boston University (Irene Simkin, Manager) or obtained from the National Cell Repository for Alzheimer{\textquoteright}s Disease (NCRAD) at Indiana University funded by NIA (U24-AG021886). We would also like to thank Dr. John Leszyk at the Proteomics and Mass Spectrometry Facility, University of Massachusetts Medical School. Funding Information: This study was funded in-part by grants from the National Institute on Aging (NIA, R01-AG048927, U01-AG032984, P30-AG13846, and RF1-AG054199) and Alzheimer?s Association (DVT-14320835 and AARF-16442664). Biological samples used in this study were prepared by the Molecular Genetics Core Facility at Boston University (Irene Simkin, Manager) or obtained from the National Cell Repository for Alzheimer?s Disease (NCRAD) at Indiana University funded by NIA (U24-AG021886). We would also like to thank Dr. John Leszyk at the Proteomics and Mass Spectrometry Facility, University of Massachusetts Medical School. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = jun,
day = "1",
doi = "10.1007/s11481-018-9781-x",
language = "English (US)",
volume = "13",
pages = "254--264",
journal = "Journal of Neuroimmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",
number = "2",
}