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2023 Alzheimer’s Association Leveraging Model & Data Resources to Advance Alzheimer’s and Dementia Discovery Program (ALZDISCOVERY)

Evaluation of Alzheimer's Endophenotype Networks Between Human and Mouse

Can the study of inherited traits help identify novel gene and protein targets for Alzheimer’s therapies?

Feixiong Cheng, Ph.D.
Cleveland Clinic Foundation
Cleveland, OH - United States


Alzheimer’s is a complex disorder that involves multiple biological processes in the brain. Some of these processes, known as “intermediate endophenotypes,” are genetically inherited (gene changes pass down from generation to generation) and can begin to change early on in the disease, before memory loss and other clinical symptoms become evident. They include brain inflammation and the clumping of disease-related tau and beta-amyloid proteins. 

In earlier studies, Dr. Feixiong Cheng and colleagues have been using sophisticated computational techniques called “multi-omics” to analyze intermediate endophenotypes in individuals who had Alzheimer’s and in genetically-engineered Alzheimer’s-like mice. This work involved genomics (the study of all the genes in an organism), proteomics (the study of the structure and functions of proteins made by cells) and transcriptomics (the study of how gene activity is turned “on” or “off” within a cell). Initial results found a number of gene and protein variations in mice that were also found in individuals with late-stage Alzheimer’s. Such variations could be used as targets for future Alzheimer’s therapies.

Research Plan

Dr. Cheng and colleagues will now  study Alzheimer’s endophenotypes in humans and mice  to locate more genes and proteins that can be targeted in clinical trials for potential disease therapies.They will then conduct similar experiments to find genes linked specifically to microglia (the immune cells of the brain). Such work could identify novel drug targets for inflammation and other microglia-related endophenotypes in Alzheimer’s.  


Dr. Chang’s project will shed new light on the role of endophenotypes in Alzheimer’s and could also lead to novel therapies for the disease. 

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