ArticleeLife2021
NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Nature communications · 2026Article
- CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk.Nature communications · 2026Article
- Group 1 mGluR stimulation rescues APOE4-mediated translation defects in neurons.Life science alliance · 2026Article
- A Model for the Development of Alzheimer's Disease.Genomics, proteomics & bioinformatics · 2025Article
- From synaptic guardian to neurodegenerative culprit: rewiring the amyloid-β feedback loop in Alzheimer's disease.The Journal of clinical investigation · 2025Review
- 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
- Alterations in the NaCerebellum (London, England) · 2025Article
- Apolipoprotein E in Alzheimer's disease: molecular insights and therapeutic opportunities.Molecular neurodegeneration · 2025Review
- Loss of the proton-activated chloride channel in neurons impairs AMPA receptor endocytosis and LTD via endosomal hyper-acidification.Cell reports · 2025Article
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer's Disease.International journal of biological sciences · 2025Review
- Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Aging Apolipoprotein E4 Mice Alters Their Brains' Inflammatory Profiles.International journal of molecular sciences · 2024Article
- APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.EMBO molecular medicine · 2024Article
- Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Elucidating the Functional Roles of Long Non-Coding RNAs in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- The Role of X Chromosome in Alzheimer's Disease Genetics.medRxiv : the preprint server for health sciences · 2024Article
- Cell type-specific functions of Alzheimer's disease endocytic risk genes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- The cell biology of APOE in the brain.Trends in cell biology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Apolipoprotein E4 (ApoE4) is the most important and prevalent risk factor for late-onset Alzheimer's disease (AD). The isoelectric point of ApoE4 matches the pH of the early endosome (EE), causing its delayed dissociation from ApoE receptors and hence impaired endolysosomal trafficking, disruption of synaptic homeostasis, and reduced amyloid clearance. We have shown that enhancing endosomal acidification by inhibiting the EE-specific sodium-hydrogen exchanger 6 (NHE6) restores vesicular trafficking and normalizes synaptic homeostasis. Remarkably and unexpectedly, loss of NHE6 (encoded by the gene
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What OpenQuestion holds
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 OpenQuestion graph.