Small Molecules to Improve Myelination in Alzheimer's Disease and APOE4 Carriers

The present disclosure provides methods of inhibiting amyloid synthesis in a subject using cyclodextrin and analogs thereof. Small molecules (cyclodextrin) reverse APOE4-associated cholesterol phenotypes and lead to significantly improved myelination both human in vitro cultures and APOE4 targeted replacement mice. This demonstrates that APOE4 alters cholesterol synthesis and transport in oligodendrocytes which impairs myelination. Collectively, this work uncovers a pathogenic role of APOE4 in oligodendrocytes and myelination and enables therapeutic opportunities for Alzheimer's Disease.

Researchers

Li-Huei Tsai / Manolis Kellis / Joel Blanchard / Jose Davila Velderrain / Leyla Akay / Djuna von Maydell / Audrey Effenberger / Matheus Victor

Departments: DLC Heads Science, Dept of Electrical Engineering & Computer Science, Brain and Cognitive Sciences, Picower Institute for Learning & Memory
Technology Areas: Therapeutics: Small Molecules
Impact Areas: Healthy Living

  • apoe4 impairs myelination via altered cholesterol biosynthesis and transport in neuronal cells
    Patent Cooperation Treaty | Published application
  • apoe4 impairs myelination via altered cholesterol biosynthesis and transport in neuronal cells
    United States of America | Published application

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