ArticleJournal of cell science2022
Isoform-dependent lysosomal degradation and internalization of apolipoprotein E requires autophagy proteins.
Article in Journal of cell science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- Huntingtin knockdown dysregulates autophagic degradation of Apolipoprotein E.Journal of Huntington's disease · 2026Article
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- Review
- The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.Cell death discovery · 2025Review
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- Review
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- The endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 3 attenuates the unfolded protein response and has pro-survival and pro-viral roles in hepatoma cells and hepatocellular carcinoma patients.Journal of biomedical science · 2025Article
- Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.PLoS computational biology · 2024Article
- iPSC-derived blood-brain barrier modeling reveals APOE isoform-dependent interactions with amyloid beta.Fluids and barriers of the CNS · 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
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.bioRxiv : the preprint server for biology · 2024Article
- The cell biology of APOE in the brain.Trends in cell biology · 2024Review
- Cell type-specific roles of APOE4 in Alzheimer disease.Nature reviews. Neuroscience · 2024Review
- Chaperone-mediated autophagy: Molecular mechanisms, biological functions, and diseases.MedComm · 2023Review
- Apolipoprotein E intersects with amyloid-β within neurons.Life science alliance · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The human apolipoprotein E4 isoform (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), and lysosomal dysfunction has been implicated in AD pathogenesis. We found, by examining cells stably expressing each APOE isoform, that APOE4 increases lysosomal trafficking, accumulates in enlarged lysosomes and late endosomes, alters autophagic flux and the abundance of autophagy proteins and lipid droplets, and alters the proteomic contents of lysosomes following internalization. We investigated APOE-related lysosomal trafficking further in cell culture, and found that APOE from the post-Golgi compartment is degraded through autophagy. We found that this autophagic process requires the lysosomal membrane protein LAMP2 in immortalized neuron-like and hepatic cells, and in mouse brain tissue. Several macroautophagy-associated proteins were also required for autophagic degradation and internalization of APOE in hepatic cells. The dysregulated autophagic flux and lysosomal trafficking of APOE4 that we observed suggest a possible novel mechanism that might contribute to AD pathogenesis. This article has an associated First Person interview with the first author of the paper.
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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 OpenQuestion graph.