ArticleAging cell2022
Alzheimer's disease associated AKAP9 I2558M mutation alters posttranslational modification and interactome of tau and cellular functions in CRISPR-edited human neuronal cells.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Genetic and environmental risk factors for dementia in African adults: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Human iPSC models revealResearch square · 2026Article
- GWAS of Tau-Neurodegeneration Mismatch Identifies New Risk Loci for Susceptibility to Tau.CNS neuroscience & therapeutics · 2026Article
- Golgi organization regulates stem cell function in the small intestine.Nature communications · 2026Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- A Novel Missense Variant in SORBS2 Is Causative With Familial Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Article
- The role of A-kinase anchoring proteins in cardiovascular diseases and recent advances.Frontiers in cell and developmental biology · 2025Review
- Missense and loss-of-function variants at GWAS loci in familial Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Real-Time Analysis of Neuronal Cell Cultures for CNS Drug Discovery.Brain sciences · 2024Article
- Chrysophanol improves memory impairment and cell injury by reducing the level of ferroptosis in A3 Biotech · 2023Article
- Genetics of Alzheimer's Disease in the African American Population.Journal of clinical medicine · 2023Review
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a pervasive neurodegeneration disease with high heritability. In this study, we employed CRISPR-Cas9-engineered technology to investigate the effects of a rare mutation (rs144662445) in the A kinase anchoring protein 9 (AKAP9) gene, which is associated with AD in African Americans (AA), on tau pathology and the tau interactome in SH-SY5Y P301L neuron-like cells. The mutation significantly increased the level of phosphorylated tau, specifically at the site Ser396/Ser404. Moreover, analyses of the tau interactome measured by affinity purification-mass spectrometry revealed that differentially expressed tau-interacting proteins in AKAP9 mutant cells were associated with RNA translation, RNA localization and oxidative activity, recapitulating the tau interactome signature previously reported with human AD brain samples. Importantly, these results were further validated by functional studies showing a significant reduction in protein synthesis activity and excessive oxidative stress in AKAP9 mutant compared with wild type cells in a tau-dependent manner, which are mirrored with pathological phenotype frequently seen in AD. Our results demonstrated specific effects of rs14462445 on mis-processing of tau and suggest a potential role of AKAP9 in AD pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.