2023 Endolysosomal Activity in Alzheimer’s (E2A)

Neuroproteasomes modulate endosome trafficking and processing

How does the brain’s nutrient transportation system contribute to beta amyloid plaque accumulation in Alzheimer’s?

Kapil Ramachandran, Ph.D.
The Trustees of Columbia University in the City of New York
New York, NY - United States

Background

Brain cells take up and transport nutrients, small molecules, and proteins through a process called “endocytosis” where material are packaged into “endosomes” which carry this material into the cell. Endosomes are critical to the normal function of brain cells but become enlarged and abnormally accumulate in the brain in Alzheimer’s. Studies have shown that changes in endosome function may be associated with the accumulation of beta amyloid plaques, one of the hallmark brain changes in Alzheimer’s. However, the mechanisms by which endocytosis becomes impaired in Alzheimer’s is unknown. 

Research Plan

Dr. Kapil Ramachandran and colleagues will examine the mechanisms by which changes in endosome function are linked to beta amyloid plaque accumulation in Alzheimer’s. They will use nerve cells grown in a laboratory dish to study how inhibiting neuroproteasomes, or how proteins are recycled in the brain, impacts how endosomes are formed and processing of Amyloid Precursor Protein, the protein that forms beta amyloid. Then the researchers will identify whether a specific group of proteins in the endocytosis pathway called the “retromer” are responsible for impaired endocytosis in Alzheimer’s.

Impact

The results of this study may shed new light on the association between impaired endocytosis and Alzheimer’s. If successful, the findings could give rise to potential new therapies to prevent or slow down the hallmark brain changes in Alzheimer’s.