2024 Alzheimer's Association Research Grant (AARG)
Cis proline kinase in the development and therapy of Alzheimer's disease
Could targeting a specific protein hold the key to preventing the hallmark brain changes in Alzheimer’s?
Chenxi Qiu, Ph.D.
Beth Israel Deaconess Medical Center
Boston, MA - United States
Background
The accumulation of amyloid-beta and tau protein to form amyloid plaques and tau tangles, respectively, are two of the hallmark brain changes seen in people living with Alzheimer’s. However, the mechanisms linking these two hallmarks are not clearly understood.
Studies have shown that a specific form of tau called Cis P-tau may play a role in promoting nerve cell damage and death in Alzheimer’s. JNK3 is a protein that is responsible for Cis P-tau formation, and researchers believe it could hold the key to understanding the link between amyloid plaques and tau tangles in Alzheimer’s.
Research Plan
For their study, Dr. Chenxi Qiu and the team will examine the mechanisms linking JNK3 to amyloid plaques and Cis P-tau formation in Alzheimer’s. They will do this by increasing levels of amyloid-beta in genetically engineered Alzheimer’s-like mice that develop tau tangles and either do or do not have JNK3. Once they have identified if loss of JNK3 reduces tau tangle formation, they will test the therapeutic potential of targeting JNK3 in Alzheimer’s. The researchers will do this by administering a JNK3 inhibitor in the same genetically engineered Alzheimer’s-like mice that develop tau tangles and measuring their cognitive function.
Impact
The results of this project may shed new light on the mechanisms linking two of the hallmark brain changes in Alzheimer’s. If successful, it could also lead to new therapeutic targets for developing treatments to slow Alzheimer’s progression.