ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2018
Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 115 citations in OpenAlex.
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Interleukin-1β-Induced Inflammatory Signaling and Myelin-Related Alterations in Oligodendroglia and Schwann Cells in Multiple Sclerosis: Modulatory Effects of Ibuprofen and Flurbiprofen.Current issues in molecular biology · 2026Article
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- APOE4-Expressing Astrocytes Exhibit Parkinson's Disease-Related Pathology.Molecular neurobiology · 2026Article
- Spermidine in the aging brain: mechanisms, preclinical evidence, and clinical perspectives.Molecular biology reports · 2026Review
- Identification of small ubiquitin-related modifier (SUMO)-related genes-based biomarkers in Alzheimer's disease based on bioinformatics analysis.Scientific reports · 2026Article
- Immuno-Regulation of Brain Region-Specific Organoids Containing Isogenic Microglia-Like Cells.Advanced healthcare materials · 2026Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Impact of APOE on cerebrovascular lipid profile in Alzheimer's disease.Acta neuropathologica · 2025Article
- Astrocyte Autophagy in Neurodegenerative Diseases: Current Progress in Mechanisms and Therapeutics.Neurochemical research · 2025Review
- Bridging the molecular and clinical aspects of resveratrol in Alzheimer's disease: a review.3 Biotech · 2025Review
- Article
- Interconnections of insulin/IGF-1 signaling and autophagy abnormalities in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Severe Cognitive Decline in Long-term Care Is Related to Gut Microbiome Production of Metabolites Involved in Neurotransmission, Immunomodulation, and Autophagy.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Sex and region-specific disruption of autophagy and mitophagy in Alzheimer's disease: linking cellular dysfunction to cognitive decline.Cell death discovery · 2025Article
- Apolipoprotein E in Alzheimer's disease: molecular insights and therapeutic opportunities.Molecular neurodegeneration · 2025Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
introductionAlzheimer apolipoprotein E (APOE) ɛ4/ɛ4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to "coordinated lysosomal expression and regulation" (CLEAR) DNA motifs.
methodsAutophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either apoE3 or apoE4. Computational modeling assessed interactions between apoE and mutated apoE with CLEAR or modified DNA.
resultsThree TFEB-regulated mRNA transcripts-SQSTM, MAP1LC3B, and LAMP2-were lower in AD ɛ4/ɛ4 than in AD ɛ3/ɛ3 brains. Computational modeling predicted avid specific binding of apoE4 to CLEAR motifs. ApoE was found in cellular nuclei, and in vitro binding assays suggest competition between apoE4 and TFEB at CLEAR sites.
conclusionApoE4-CLEAR interactions may account for suppressed autophagy in APOE ɛ4/ɛ4 carriers and, in this way, contribute to earlier AD onset.
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