ArticleeLife2018
Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer's disease.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 101 citations in OpenAlex.
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- Review
- CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk.Nature communications · 2026Article
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
- Structural Change of ApoE-Lipid Nanoparticles Alters Receptor-Mediated Endocytosis and Induces Endosomal Disruption.Journal of the American Chemical Society · 2026Article
- Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease.Nature cell biology · 2026Article
- Article
- Role of apolipoprotein E4 in alzheimer's disease pathogenesis and emerging therapeutic strategies.Metabolic brain disease · 2025Review
- From synaptic guardian to neurodegenerative culprit: rewiring the amyloid-β feedback loop in Alzheimer's disease.The Journal of clinical investigation · 2025Review
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- APOE4-Aβ synergy drives brain network dysfunction and neuronal lysosomal-ER proteostasis dysregulation a preclinical Alzheimer's disease model.bioRxiv : the preprint server for biology · 2025Article
- Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel.Nature metabolism · 2025Article
- Axon Regeneration and Functional Recovery after Spinal Cord Injury is Enhanced by Allele-Specific ApoE Neuronal Action through LRP8.bioRxiv : the preprint server for biology · 2025Article
- Physical and functional interactions between LDLR family members and CXCR4 in breast cancer.The FEBS journal · 2025Article
- Understanding the role of microglia in Alzheimer's disease: insights into mechanisms, acupuncture, and potential therapeutic targets.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Review
- HYPOTHESIS: Lipid-protecting disulfide bridges are the missing molecular link between ApoE4 and sporadic Alzheimer's disease in humans.Prostaglandins, leukotrienes, and essential fatty acids · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Aging Apolipoprotein E4 Mice Alters Their Brains' Inflammatory Profiles.International journal of molecular sciences · 2024Article
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.PLoS computational biology · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
ApoE4 genotype is the most prevalent and also clinically most important risk factor for late-onset Alzheimer's disease (AD). Available evidence suggests that the root cause for this increased risk is a trafficking defect at the level of the early endosome. ApoE4 differs from the most common ApoE3 isoform by a single amino acid that increases its isoelectric point and promotes unfolding of ApoE4 upon endosomal vesicle acidification. We found that pharmacological and genetic inhibition of NHE6, the primary proton leak channel in the early endosome, in rodents completely reverses the ApoE4-induced recycling block of the ApoE receptor Apoer2/Lrp8 and the AMPA- and NMDA-type glutamate receptors that are regulated by, and co-endocytosed in a complex with, Apoer2. Moreover, NHE6 inhibition restores the Reelin-mediated modulation of excitatory synapses that is impaired by ApoE4. Our findings suggest a novel potential approach for the prevention of late-onset AD.
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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 Socratic graph.