- Home
- About
- Collaborative Data Access (SAGs)
- Publications
- For Members
Title | Tau Phosphorylation is Impacted by Rare AKAP9 Mutations Associated with Alzheimer Disease in African Americans. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Ikezu T, Chen CD, DeLeo AM, Zeldich E, M Fallin D, Kanaan NM, Lunetta KL, Abraham CR, Logue MW, Farrer LA |
Journal | J Neuroimmune Pharmacol |
Volume | 13 |
Issue | 2 |
Pagination | 254-264 |
Date Published | 06/2018 |
ISSN | 1557-1904 |
Keywords | A Kinase Anchor Proteins, Aged, Alzheimer Disease, Black or African American, Cytoskeletal Proteins, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Mutation, Missense, Phosphorylation, Protein Processing, Post-Translational, tau Proteins |
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, Aβ, and total and T181 phospho-Tau (pTau). AKAP9 mutations had no effect on Aβ/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. |
DOI | 10.1007/s11481-018-9781-x |
Alternate Journal | J Neuroimmune Pharmacol |
PubMed ID | 29516269 |
PubMed Central ID | PMC5928172 |
Grant List | RF1 AG054199 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States R01 AG048927 / AG / NIA NIH HHS / United States RF1 AG057519 / AG / NIA NIH HHS / United States |