Massachusetts Institute of Technology

Matheus Victor

Li-Huei Tsai

Manolis Kellis

Joel Blanchard

Jose Davila Velderrain

Leyla Akay

Djuna Von Maydell

Audrey Effenberger

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.

APOE4 impairs myelination via altered cholesterol biosynthesis and transport in oligodendroglia

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Cambridge, MA, United States of America

Matheus Victor