ArticleActa neuropathologica2021
Apolipoprotein E regulates lipid metabolism and α-synuclein pathology in human iPSC-derived cerebral organoids.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 3 of them syntheses that pooled it.
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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
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Spatial lipidomics of the human brain: systematic review of current state and future perspectives.Molecular psychiatry · 2026Pooled it
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.Journal of translational medicine · 2023Pooled it
- Cholesterol dysregulation in APOE4 astrocytes promotes α-synuclein pathology in miBrains.Cell stem cell · 2026Article
- Understanding the genetic imperfections of Lewy body dementia.Molecular neurodegeneration · 2026Review
- Extracellular vesicle-mediated bidirectional communication between the brain and peripheral organs in Alzheimer's disease: evidence, mechanisms, and translational perspectives.Journal of nanobiotechnology · 2026Review
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β- catenin signaling for Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2026Article
- Glial pathology networks reveal early olfactory vulnerability in post mortem human Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- Immunosenescence and organoids: pathophysiology and therapeutic opportunities.Immunity & ageing : I & A · 2025Review
- Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.The FEBS journal · 2025Review
- GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau.Nature communications · 2025Article
- Cholesterol-mediated Lysosomal Dysfunction inbioRxiv : the preprint server for biology · 2025Article
- The role ofFrontiers in neuroscience · 2025Review
- Potential Use of Organoids in Regenerative Medicine.Tissue engineering and regenerative medicine · 2024Review
- Integrative analysis of causal associations between neurodegenerative diseases and colorectal cancer.Heliyon · 2024Article
- ABCA7 deficiency causes neuronal dysregulation by altering mitochondrial lipid metabolism.Molecular psychiatry · 2024Article
- Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review.International journal of molecular sciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
APOE4 is a strong genetic risk factor for Alzheimer's disease and Dementia with Lewy bodies; however, how its expression impacts pathogenic pathways in a human-relevant system is not clear. Here using human iPSC-derived cerebral organoid models, we find that APOE deletion increases α-synuclein (αSyn) accumulation accompanied with synaptic loss, reduction of GBA levels, lipid droplet accumulation and dysregulation of intracellular organelles. These phenotypes are partially rescued by exogenous apoE2 and apoE3, but not apoE4. Lipidomics analysis detects the increased fatty acid utilization and cholesterol ester accumulation in apoE-deficient cerebral organoids. Furthermore, APOE4 cerebral organoids have increased αSyn accumulation compared to those with APOE3. Carrying APOE4 also increases apoE association with Lewy bodies in postmortem brains from patients with Lewy body disease. Our findings reveal the predominant role of apoE in lipid metabolism and αSyn pathology in iPSC-derived cerebral organoids, providing mechanistic insights into how APOE4 drives the risk for synucleinopathies.
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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.