2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

A CRISPR-Based Therapeutic for Alzheimer's disease

Can gene editing reduce levels of harmful beta-amyloid in the brain?

Brent Aulston, Ph.D.
University of California, San Diego
La Jolla, CA - United States

Background

One of the hallmarks of Alzheimer’s is the accumulation of high levels of beta-amyloid protein fragments into plaques in the brain. Beta-amyloid is produced from a “parent” protein named amyloid precursor protein (APP). Specific proteins called enzymes inside nerve cells cut APP into fragments. Depending on how the enzymes cut it, APP can create harmful beta-amyloid protein fragments or longer amyloid fragments that have been associated with improved brain health. 

Dr. Brent Aulston and colleagues have developed a new gene therapy technique that specifically targets APP. Their approach uses a gene editing system called CRISPR to decrease the production of harmful beta-amyloid and promote the production of longer, protective amyloid fragments.

Research Plan

Dr. Aulston and colleagues will study the safety and efficacy of their gene therapy in genetically engineered Alzheimer’s-like mice that develop beta-amyloid plaques in their brains. Following administration of the gene therapy, the researchers will study how the treatment impacts cognition and brain changes using behavioral tests as well as conduct microscopic investigations of brain changes in the genetically engineered mice and cognitively unimpaired mice.

Impact

If successful, the results may pave the way for future studies of this novel gene therapy in humans.