ArticlePNAS nexus2026
APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.
Article in PNAS nexus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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
3 citing papers in PubMed.
- From astrocyte cholesterol synthesis to synaptic dysfunction: mechanisms of neuron-glia lipid coupling.Molecular biology reports · 2026Review
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
Corrections and comments
- Update of
Authors and funding
6 authors.
Funding
Abstract
Lipid abnormalities are emerging as key pathogenic mechanisms in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Astrocytes in the brain provide apolipoprotein E (APOE) proteins and influence neuronal metabolism and health. Using live-cell imaging and objective neurite imaging techniques, we induced cellular lipid load (cholesterol and triglycerides) by inhibiting the lysosomal cholesterol transport protein NPC1 in human neuron-astrocyte cocultures and examined the effects of CRISPR-edited APOE3 and APOE4 human astrocytes on the rescue of dystrophic neurites, where axons and dendrites of nerve cells become disfigured. APOE3, but not APOE4 or APOE knockout, astrocytes prevented cholesterol- and lipid-induced neurite damage in APOE4 neurons. In the media of APOE3 neuron-astrocyte cocultures, high-density lipoprotein-like particles were larger and presumably more lipidated than those in equivalent APOE4 cocultures. This discovery highlights that living APOE3 astrocytes control key biological mechanisms by physiologically enhancing lipid cellular homeostasis and rescuing lipid-induced neurite structural abnormalities relevant to Alzheimer's disease and neurodegenerative diseases.
Identifiers
What Socratic 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 Socratic graph.