Molecular and Cellular Physiopathology of Parkinson's Disease

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are two neurodegenerative disorders resulting from environmental and genetic factors. For some patients, usually those with a familial form, the disease is caused by a mutation in a single gene. About 20 such genes are known to contribute to PD, and three to AD. Nevertheless, the sequencing of these genes with current techniques does not provide a diagnosis for the vast majority of cases. Further, genetic variations that partially increase or reduce risk are not completely understood for AD and PD.

Recently, cutting-edge technologies have emerged, such as long-read sequencing (LRS), that can help us better understand genetic risk in PD and AD. Not only do these new approaches allow us to identify complex mutations that were previously undetectable, they also help us understand the biological significance of human genetic variations. Using these new technologies, multiple biological data types (LRS, blood protein levels, etc.) were generated in healthy older controls and PD and AD patients from two cohorts: the Paris Brain Institute (n=140) and the Stanford’s Alzheimer’s Disease Research Center (n=600). We believe the joint analysis of these two cohorts will enhance understanding of the genetic landscape of PD and AD.