ArticleJournal of Alzheimer's disease : JAD2019
The Effects of APOE4 on Mitochondrial Dynamics and Proteins in vivo.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Review
- Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice.Neurochemical research · 2026Article
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
- APOE4-Expressing Astrocytes Exhibit Parkinson's Disease-Related Pathology.Molecular neurobiology · 2026Article
- Review
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- Immuno-Regulation of Brain Region-Specific Organoids Containing Isogenic Microglia-Like Cells.Advanced healthcare materials · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Mitochondrial dysfunction in Alzheimer's disease and related sex differences.Frontiers in aging neuroscience · 2026Review
- Role of apolipoprotein E4 in alzheimer's disease pathogenesis and emerging therapeutic strategies.Metabolic brain disease · 2025Review
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.EMBO molecular medicine · 2024Article
- Mitochondrial Dynamics in Brain Cells During Normal and Pathological Aging.International journal of molecular sciences · 2024Review
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Insulin Resistance, a Risk Factor for Alzheimer's Disease: Pathological Mechanisms and a New Proposal for a Preventive Therapeutic Approach.Biomedicines · 2024Review
- The duality of amyloid-β: its role in normal and Alzheimer's disease states.Molecular brain · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
This study examined the effects of apolipoprotein E4 (APOE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), on proteins involved in mitochondrial dynamics and autophagy, in the hippocampus of targeted replacement mice. Immunohistochemical measurements revealed that the levels of the mitochondrial fusion-mediating protein, MFN1, were higher, whereas those of corresponding fission-regulating protein, DRP-1, were lower in the hippocampus of ApoE4 mice than in the corresponding ApoE3 mice, indicating that APOE4 is associated with increased mitochondrial fusion and decreased fission. A similar ApoE4-driven decrease in DRP-1 was also observed in AD brains. The levels of the mitochondrial proteins COX1 and Tom40, were higher in the ApoE4 mice, which is consistent with the increased fusion. Measurements of the levels of cleaved PINK1 and parkin, which mark and target mitochondria for mitophagic degradation, revealed lower levels of cleaved PINK1, suggesting reduced mitochondrial membrane potential, and higher levels of parkin in the hippocampus of ApoE4 compared with the ApoE3 mice, indicating altered mitophagy. The levels of the ubiquitin-binding scaffold protein, p62/SQSTM1, which directs selected cargo to the autophagosomes, were also higher in the ApoE4 mice. These findings suggest that APOE4 is associated with enhanced mitochondrial fusion and decreased fission. Additionally, the results indicate that mitophagy/autophagy is reduced in ApoE4 mice, resulting in higher levels of proteins such as parkin and p62, which are normally degraded during this process. Taken together, these results suggest a novel mechanism that may underlie the pathological effects of APOE4 and indicate that use of APOE4 genotyping could pave the way for identification of novel APOE4-related therapeutic targets.
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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.