ArticleProceedings of the National Academy of Sciences of the United States of America2018
Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Histone deacetylase-mediated regulation of endolysosomal pH.The Journal of biological chemistry · 2018Pooled it
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.Nature communications · 2026Article
- Unraveling Neurodegeneration: Common Molecular Mechanisms and Novel Therapeutic Concepts in Major Neurodegenerative Disorders.Brain and behavior · 2026Review
- HDAC7 acts as an astrocytic mediator of Aβ pathology that directly engages IKK to drive astrocyte neurotoxicity and neurodegeneration in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Epigenetic Modulation Is a Key Mechanism in Cognitive Deficit: Unveiling Garcinol as a Potent HAT Inhibitor in Improving Alzheimer's Disease.ACS omega · 2026Review
- Targeting the HDAC4-NHE6-endosomal pH axis restores amyloid-β clearance and cognitive function in Alzheimer's disease mice.Journal of nanobiotechnology · 2026Article
- Structural Change of ApoE-Lipid Nanoparticles Alters Receptor-Mediated Endocytosis and Induces Endosomal Disruption.Journal of the American Chemical Society · 2026Article
- Amyloid-Frontiers in neuroscience · 2026Review
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- The Christianson syndrome protein, sodium hydrogen exchanger isoform 6, is required for fat accumulation.The Journal of physiology · 2025Article
- Histone Deacetylases in Neurodegenerative Diseases and Their Potential Role as Therapeutic Targets: Shedding Light on Astrocytes.Pharmaceuticals (Basel, Switzerland) · 2025Review
- ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells.Stem cell reports · 2025Article
- Review
- Short-term exposure to polystyrene microplastics alters cognition, immune, and metabolic markers in an apolipoprotein E (APOE) genotype and sex-dependent manner.Environmental research communications · 2025Article
- Article
- Lysosomal acidification impairment in astrocyte-mediated neuroinflammation.Journal of neuroinflammation · 2025Review
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Endosomes have emerged as a central hub and pathogenic driver of Alzheimer's disease (AD). The earliest brain cytopathology in neurodegeneration, occurring decades before amyloid plaques and cognitive decline, is an expansion in the size and number of endosomal compartments. The strongest genetic risk factor for sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4). Previous studies have shown that ApoE4 potentiates presymptomatic endosomal dysfunction and defective endocytic clearance of amyloid beta (Aβ), although how these two pathways are linked at a cellular and mechanistic level has been unclear. Here, we show that aberrant endosomal acidification in ApoE4 astrocytes traps the low-density lipoprotein receptor-related protein (LRP1) within intracellular compartments, leading to loss of surface expression and Aβ clearance. Pathological endosome acidification is caused by ε4 risk allele-selective down-regulation of the Na
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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.