Funded Studies Details

2019 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Generation of Human Cerebral Organoids to Model Alzheimer’s Disease

What strategies help cells clear abnormal tau and beta-amyloid proteins from the brain in Alzheimer’s?

 

Luz Karina Cuanalo Contreras, Ph.D.
Northwestern University
Evanston, IL - United States

Background

The “proteostasis network” is a collection of strategies cells use to maintain healthy proteins. It helps cells make proteins, and ensures they function properly. Cells also use the proteostasis network to remove damaged proteins, like abnormal beta-amyloid and tau proteins that form plaques and tangles respectively, both hallmarks of Alzheimer’s. As people age, the proteostasis network becomes less effective. Strategies to improve the proteostasis network might be one way to help cells manage proteins that accumulate in the brain during Alzheimer’s disease.
 

Research Plan

Dr. Karina Cuanalo-Contreras and colleagues are studying ways to improve proteostasis network functions in two Alzheimer’s laboratory models. In the first portion of the study, the researchers will use small worms that have been genetically modified to make abnormal tau and beta-amyloid proteins. The researchers will expose the worms to specific stress conditions (that are unusual and not normally faced by the cell) that target different parts of the proteostasis network, and measure how tau and beta-amyloid accumulates. This will help Dr. Cuanalo-Contreras understand which parts of the proteostasis network might most influence protein accumulation during Alzheimer’s.
 
In the second part of the study, Dr. Cuanalo-Contreras’ team will use nerve cells growing in laboratory dishes, from people who had Alzheimer’s dementia as well as cognitively unimpaired individuals. The researchers will compare how the cells alter genes; these genes provide instructions on how to respond to different types of unusual conditions not normally faced by the cell. Dr. Cuanalo-Contreras’ goal is to identify exactly how the proteostasis network may be impacted in Alzheimer’s.

 

Impact

The study results could help provide insights into the biological mechanisms contributing to age-related brain degeneration. This study could lay the foundation for therapies designed to prevent abnormal tau or beta-amyloid proteins from accumulating in the brains of people with Alzheimer’s.