ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Decreased peripheral brain-derived neurotrophic factor levels in Alzheimer's disease: a meta-analysis study (N=7277).Molecular psychiatry · 2017Pooled it
- Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer's Disease Phase IIa and Expanded Access Trials.Journal of Alzheimer's disease : JAD · 2017Trial
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Parent-of-origin effects in Alzheimer's liability dissociate neurocognitive and cardiovascular traits in at-risk individuals.Cell reports. Medicine · 2026Article
- HDAC3 in Alzheimer's Disease: established evidence, unresolved questions, and translational priorities.Molecular biology reports · 2026Review
- Targeting the HDAC4-NHE6-endosomal pH axis restores amyloid-β clearance and cognitive function in Alzheimer's disease mice.Journal of nanobiotechnology · 2026Article
- Amyloid β Instigates Cardiac Neurotrophic Signaling Impairment, Driving Alzheimer's Associated Heart Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dexmedetomidine as a potential neuroprotective agent against Alzheimer's disease: molecular mechanisms and therapeutic perspectives.Frontiers in aging neuroscience · 2026Review
- N-terminal oligomerization drives HDAC4 nuclear condensation and neurodevelopmental dysfunction inOpen biology · 2025Article
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Body Circumference and Cognitive Function: Role of Apolipoprotein E ε4 in the Elderly.International journal of molecular sciences · 2025Article
- BDNF/proBDNF Interplay in the Mediation of Neuronal Apoptotic Mechanisms in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Unlocking Alzheimer's Disease: The Role of BDNF Signaling in Neuropathology and Treatment.Neuromolecular medicine · 2025Review
- Peripheral tissue BDNF expression is affected by promoter IV defect and enriched environments in mice: negative hippocampus-intestine and positive thymus-serum-muscle correlations.Molecular medicine (Cambridge, Mass.) · 2025Article
- Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis.Science advances · 2024Article
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- APOE-NOTCH axis governs elastogenesis during human cardiac valve remodeling.Nature cardiovascular research · 2024Article
- Comprehensive characterization of the neurogenic and neuroprotective action of a novel TrkB agonist using mouse and human stem cell models of Alzheimer's disease.Stem cell research & therapy · 2024Article
- A novel insight into neurological disorders through HDAC6 protein-protein interactions.Scientific reports · 2024Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for several neurodegenerative disorders, including Alzheimer's disease (AD). Epigenetic dysregulation, including aberrations in histone acetylation, is also associated with AD. We show here for the first time that ApoE4 increases nuclear translocation of histone deacetylases (HDACs) in human neurons, thereby reducing BDNF expression, whereas ApoE3 increases histone 3 acetylation and upregulates BDNF expression. Amyloid-β (Aβ) oligomers, which have been implicated in AD, caused effects similar to ApoE4. Blocking low-density lipoprotein receptor-related protein 1 (LRP-1) receptor with receptor-associated protein (RAP) or LRP-1 siRNA abolished the ApoE effects. ApoE3 also induced expression of protein kinase C ε (PKCε) and PKCε retained HDACs in the cytosol. PKCε activation and ApoE3 supplementation prevented ApoE4-mediated BDNF downregulation. PKCε activation also reversed Aβ oligomer- and ApoE4-induced nuclear import of HDACs, preventing the loss in BDNF. ApoE4 induced HDAC6-BDNF promoter IV binding, which reduced BDNF exon IV expression. Nuclear HDAC4 and HDAC6 were more abundant in the hippocampus of ApoE4 transgenic mice than in ApoE3 transgenic mice or wild-type controls. Nuclear translocation of HDA6 was also elevated in the hippocampus of AD patients compared with age-matched controls. These results provide new insight into the cause of synaptic loss that is the most important pathologic correlate of cognitive deficits in AD.
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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.