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

Departments: DLC Heads Science, Picower Institute for Learning & Memory, Brain and Cognitive Sciences, Dept of Electrical Engineering & Computer Science
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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