Chengran Yang, a PhD candidate in the lab of Carlos Cruchaga, is the first author of a manuscript just published in the prestigious journal Nature Neuroscience. He used multi-tissue proteomics to identify hundreds of proteins that are genetically regulated. By using statistical methods, such as Mendelian randomization, he was able to implicate several of these proteins as causative factors for neurodegenerative diseases, including Alzheimer disease, Parkinson disease, frontotemporal dementia, or stroke. Using conditional analysis, he was able to identify independent protein quantitative trait loci (pQTLs), finding over 40 proteins affected by at least 3 pQTLs and highlighting the complexity of some genetic regions. This work constitutes the largest analysis of brain and cerebrospinal fluid pQTL ever completed.
This research has several implications for the future of Alzheimer disease. These gene loci can be sequenced to predict an individual’s disease risk, and the proteins may be viable drug targets for the treatment of disease. By understanding the changes in the genes responsible for altering protein levels, genetic tests will become better at predicting Alzheimer disease risk. The authors of the manuscript identified several FDA approved drugs that are known to target proteins in important pathways uncovered by the work. These drugs have already been determined to be safe and may be repositioned to treat Alzheimer disease, or other neurodegenerative diseases, and bypass early phase clinical trials.
Chengran’s work has now been covered by the Washington University School of Medicine’s publication, the SOURCE.
The full-text publication can be found at Nature Neuroscience: https://www.nature.com/articles/s41593-021-00886-6