ArticleSignal transduction and targeted therapy2021
A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
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- Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.Biological psychiatry · 2023Pooled it
- Convergent mitochondrial impairment and apoptosis driven by simultaneous down-regulation of multiple genes at 11p11.2 in Alzheimer's disease.Molecular psychiatry · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- The Interplay of Aging, Synaptic Proteins, and Microglial Accumulation.Neuroscience bulletin · 2026Article
- Ingenane Diterpenoids fromMolecules (Basel, Switzerland) · 2026Article
- Integrated Multi-Omics Analysis Reveals Dysregulated Lipid Metabolism as a Novel Mechanism in Androgenetic Alopecia.Biomedicines · 2026Article
- Next questions of autophagy in neurodegenerative diseases: From mechanisms to therapeutics.Innovation (Cambridge (Mass.)) · 2026Review
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- GTsurvival: A Hybrid GCN-Neural Decision Tree Model for Restricted Mean Survival Time Prediction with Complex Censored Data.Entropy (Basel, Switzerland) · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- The genetic landscape of early-onset Alzheimer's disease in China.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Piezo2 Contributes to Traumatic Brain Injury by Activating the RhoA/ROCK1 Pathways.Molecular neurobiology · 2024Article
- GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.Cellular & molecular immunology · 2024Article
- Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase.Molecular psychiatry · 2024Article
- Autophagy, a double-edged sword for oral tissue regeneration.Journal of advanced research · 2024Review
- Association analysis between Acetyl-Coenzyme A Acyltransferase-1 gene polymorphism and growth traits in Xiangsu pigs.Frontiers in genetics · 2024Article
- Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
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- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-β (Aβ) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including APP, PSEN1, and PSEN2 impair a variety of pathways, including protein processing, axonal transport, and metabolic homeostasis. Here we identified a missense variant rs117916664 (c.896T>C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (ACAA1) gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the Aβ pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.
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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.