Researchers in the Taub Institute at Columbia University Medical Center (CUMC) have identified a mechanism that appears to underlie the common sporadic (non-familial) form of Parkinson’s disease. The discovery highlights potential new therapeutic targets for Parkinson’s and could lead to a blood test for the disease. The study, based mainly on analysis of human brain tissue, was published September 25th in the online edition of Nature Communications.
Using a variety of techniques, including gene-expression analysis and gene-network mapping, the CUMC researchers discovered how common forms of alpha-synuclein contribute to sporadic Parkinson’s. “It turns out multiple different alpha-synuclein transcript forms are generated during the initial step in making the disease protein; our study implicates the longer transcript forms as the major culprits,” said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and neurology at CUMC. “Some very common genetic variants in the alpha-synuclein gene, present in many people, are known to impact the likelihood that an individual will suffer from sporadic Parkinson’s. In our study, we show that people with ‘bad’ variants of the gene make more of the elongated alpha-synuclein transcript forms. This ultimately means that more of the disease protein is made and may accumulate in the brain.”