Massachusetts Institute of Technology

Joel Blanchard

Li-Huei Tsai

Robert S Langer, Jr

Manolis Kellis

Adele Bubnys

Djuna Von Maydell

Alice Stanton

Leyla Akay

Audrey Effenberger

Jose Davila Velderrain

Matheus Victor

The present disclosure provides, in some embodiments, in vitro brain (miBRAIN) having functional and structural properties of in vivo brain as well as methods of identifying compounds capable of influencing brain function.

Multicellular integrated brain tissue in neurological diseases

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

The present disclosure provides methods of inhibiting amyloid synthesis in a subject using small molecule inhibitors. The invention also includes methods of treating disease associated with amyloid synthesis, such as Alzheimer's disease. The small molecule inhibitors disclosed herein are compounds which are non-immunosuppressant cyclosporin including the pharmaceutically acceptable salts thereof.

Small molecule suppressors of APOE gene expression and cerebral vascular amyloid pathology

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Arlington, MA, United States of America

Joel Blanchard