ArticleCell2025
Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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.
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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
55 citing papers in PubMed.
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.Nature communications · 2026Article
- Cholesterol dysregulation in APOE4 astrocytes promotes α-synuclein pathology in miBrains.Cell stem cell · 2026Article
- USF2-Mediated APOE-Cholesterol Signaling Promotes CTC Clustering and Metastasis in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- Review
- Apolipoprotein E (Genes · 2026Article
- Turning Unpredictable Biomolecule Adsorption to Controlled Corona Formation: Focus on Carbon Nanomaterials.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Progranulin deficiency perturbs lipid metabolism in white matter microglia.bioRxiv : the preprint server for biology · 2026Article
- Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer's disease and related disorders.Molecular neurodegeneration · 2026Review
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Alzheimer disease protection from the periphery.Nature reviews. Neurology · 2026Article
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Genome-scale metabolic modeling uncovers cell-type specific signatures associated with APOE variants.iScience · 2026Article
- Lipofuscin accumulation in aging and CLN1 is associated with deficient de-S-acylation, lyso-mitochondrial dysfunction, and lipid dyshomeostasis.Acta neuropathologica · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Disrupted lipid homeostasis as a pathogenic mechanism in ABCA7-associated Alzheimer's disease risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors.
Funding
Abstract
While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation. Lipofuscin increased lysosomal accumulation of tau fibrils and was elevated in the APOE4 mouse brain with exacerbation by tau pathology. Intrahippocampal injection of PUFA-CE-lipApoE4 was sufficient to induce lipofuscinosis in wild-type mice. Finally, the protective Christchurch mutation also reduced LDLR binding and phenocopied ApoE2. Collectively, our data strongly suggest decreased lipApoE-LDLR interactions minimize LOAD risk by reducing the deleterious effects of endolysosomal targeting of ApoE and associated pathogenic lipids.
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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.