--- title: How the biggest Alzheimer’s risk gene disrupts the... description: MIT researchers identified why the APOE4 gene variant, the biggest genetic risk factor for Alzheimer's, disrupts myelination of neurons. A genome-wide CRISPR... canonical: https://daily.dev/posts/how-the-biggest-alzheimer-s-risk-gene-disrupts-the-process-of-insulating-neurons-tzy31szu5 twitter:card: summary_large_image twitter:site: @dailydotdev og:type: website og:site_name: daily.dev og:title: How the biggest Alzheimer’s risk gene disrupts the process of insulating neurons | daily.dev og:description: MIT researchers identified why the APOE4 gene variant, the biggest genetic risk factor for Alzheimer's, disrupts myelination of neurons. A genome-wide CRISPR... og:url: https://daily.dev/posts/how-the-biggest-alzheimer-s-risk-gene-disrupts-the-process-of-insulating-neurons-tzy31szu5 og:image: https://api.daily.dev/og/posts/tZY31sZu5.png og:image:alt: How the biggest Alzheimer’s risk gene disrupts the process of insulating neurons og:image:width: 1200 og:image:height: 630 og:locale: en --- > ## Documentation Index > Fetch the complete documentation index at: https://daily.dev/llms.txt > Use this file to discover all available pages before exploring further. # How the biggest Alzheimer’s risk gene disrupts the process of insulating neurons **[MIT News](https://daily.dev/sources/mit)** · 5 min read · 0 upvotes · 0 comments ## Summary MIT researchers identified why the APOE4 gene variant, the biggest genetic risk factor for Alzheimer's, disrupts myelination of neurons. A genome-wide CRISPR knockout screen in human APOE4-carrying oligodendrocytes showed that suppressed Wnt signaling causes lipid droplets to accumulate instead of being used to insulate neuron axons. The team traced this to reduced beta-catenin and excessive GSK3b expression, and found that inhibiting GSK3b with a chemical called CHIR99021 reduced lipid droplets and boosted myelination in cell cultures. In APOE4 mice modeling Alzheimer's tau pathology, CHIR99021 treatment reduced lipid droplets and increased myelination in the hippocampus compared to untreated controls. The study was published Oct. 15 in Cell Stem Cell, led by Li-Huei Tsai and Leyla Akay. ## Full article daily.dev links to this article rather than hosting it. Read it at the original source: ## Questions this post answers ### How does the APOE4 gene variant disrupt myelination of neurons in Alzheimer's disease? APOE4 suppresses Wnt signaling in oligodendrocytes, the cells that produce myelin, causing lipid droplets to accumulate instead of being used to insulate neuron axons. Researchers found reduced beta-catenin and excessive GSK3b expression in APOE4-carrying oligodendrocytes compared to the neutral APOE3 variant, which depresses Wnt activity and impairs myelination. _Developers tracking biomedical research breakthroughs can follow Alzheimer's mechanism studies like this on daily.dev._ ### Can inhibiting GSK3b restore myelination in APOE4-related Alzheimer's models? Yes, inhibiting GSK3b with a chemical called CHIR99021 reduced lipid droplet accumulation and increased myelination in human APOE4 oligodendrocyte and organoid cultures. In mice carrying APOE4 and modeling Alzheimer's tau pathology, CHIR99021 treatment reduced lipid droplets and increased myelination in the hippocampus compared to untreated controls. _Anyone following computational drug-target discovery can keep tabs on CRISPR-based findings like this via daily.dev._ ## Similar posts on daily.dev - [Scientists discover genetics behind leaky brain blood vessels in Rett syndrome](https://daily.dev/posts/scientists-discover-genetics-behind-leaky-brain-blood-vessels-in-rett-syndrome-a97lejb7e) · MIT News · 0 upvotes · 0 comments - [AlphaFold Reveals a Key Protein Behind Heart Disease](https://daily.dev/posts/alphafold-reveals-a-key-protein-behind-heart-disease-q6y32fk7j) · DeepMind · 1 upvotes · 0 comments - [Rett syndrome study highlights potential for personalized treatments](https://daily.dev/posts/rett-syndrome-study-highlights-potential-for-personalized-treatments-khso7nvfz) · MIT News · 0 upvotes · 0 comments - [Blood Tests Could Provide Early Warning Of Alzheimers Disease](https://daily.dev/posts/blood-tests-could-provide-early-warning-of-alzheimers-disease-0h2q4owsz) · Hackaday · 0 upvotes · 0 comments --- Tags: [#biotech](https://daily.dev/tags/biotech) [View this post on daily.dev](https://daily.dev/posts/how-the-biggest-alzheimer-s-risk-gene-disrupts-the-process-of-insulating-neurons-tzy31szu5) ```json {"@context":"https://schema.org","@graph":[{"@type":"Organization","@id":"https://daily.dev/#organization","name":"daily.dev","url":"https://daily.dev","logo":{"@type":"ImageObject","url":"https://daily.dev/apple-touch-icon.png","width":180,"height":180},"sameAs":["https://twitter.com/dailydotdev","https://github.com/dailydotdev","https://www.linkedin.com/company/daily-dev-ltd"]},{"@type":"WebSite","@id":"https://daily.dev/#website","url":"https://daily.dev","name":"daily.dev","publisher":{"@id":"https://daily.dev/#organization"},"potentialAction":{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https://daily.dev/search?q={search_term_string}"},"query-input":"required name=search_term_string"}}]} {"@context":"https://schema.org","@type":"TechArticle","headline":"How the biggest Alzheimer’s risk gene disrupts the process of insulating neurons","url":"https://daily.dev/posts/how-the-biggest-alzheimer-s-risk-gene-disrupts-the-process-of-insulating-neurons-tzy31szu5","mainEntityOfPage":{"@type":"WebPage","@id":"https://daily.dev/posts/how-the-biggest-alzheimer-s-risk-gene-disrupts-the-process-of-insulating-neurons-tzy31szu5"},"datePublished":"2026-10-28T18:30:40.150Z","dateModified":"2026-10-28T19:04:04.838Z","description":"MIT researchers identified why the APOE4 gene variant, the biggest genetic risk factor for Alzheimer's, disrupts myelination of neurons. 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Researchers found reduced beta-catenin and excessive GSK3b expression in APOE4-carrying oligodendrocytes compared to the neutral APOE3 variant, which depresses Wnt activity and impairs myelination. Developers tracking biomedical research breakthroughs can follow Alzheimer's mechanism studies like this on daily.dev."}},{"@type":"Question","name":"Can inhibiting GSK3b restore myelination in APOE4-related Alzheimer's models?","acceptedAnswer":{"@type":"Answer","text":"Yes, inhibiting GSK3b with a chemical called CHIR99021 reduced lipid droplet accumulation and increased myelination in human APOE4 oligodendrocyte and organoid cultures. In mice carrying APOE4 and modeling Alzheimer's tau pathology, CHIR99021 treatment reduced lipid droplets and increased myelination in the hippocampus compared to untreated controls. Anyone following computational drug-target discovery can keep tabs on CRISPR-based findings like this via daily.dev."}}]} ```