BERLIN—A new link has been established between superoxide dismutase 1 (SOD1) protein aggregation and neuronal loss in the Parkinson’s disease brain, according to a study released at the 20th International Congress of Parkinson’s Disease and Movement Disorders.
A trademark of many neurodegenerative diseases is abnormal accumulation of proteins in the form of deposits or aggregates. It is already known that SOD1 protein aggregation in the brain is primarily associated with neuronal loss in amyotrophic lateral sclerosis (ALS). To date, abnormal aggregation of alpha-synuclein protein into Lewy bodies is considered the primary cause of neuronal loss in Parkinson’s disease.
Benjamin G. Trist and colleagues at the University of Sydney in Australia and researchers in France sought to characterize a novel connection between SOD1 aggregation and neuronal loss in Parkinson’s disease. The researchers tested postmortem tissues from deceased patients with Parkinson’s disease and age-matched control brains and found that protein aggregates that tested positive for SOD1 were significantly more abundant in degenerating regions of the Parkinson’s disease brain ( > 5-fold increase in the substantia nigra and > 2.5-fold increase in the locus coeruleus). These findings establish a new role of SOD1 pathology in neuronal vulnerability in Parkinson’s disease.
Jeffrey H. Kordower, PhD, Professor of Neurosurgery at Rush University Medical Center and Director of the Research Center for Brain Repair in Chicago, commented, “This is a very noteworthy abstract documenting SOD1 aggregates in Parkinson’s disease. What makes this work important is the abundance of these aggregates in selectively vulnerable regions in the Parkinson’s disease brain, such as the substantia nigra and locus coeruleus, with less abundance in regions that are selectively resistant in the disease. This appears independent of alpha-synuclein pathology. What remains to be determined is whether SOD1 aggregation is a primary pathologic event or is secondary to another pathologic pathway. Still, this work suggests that multiple aggregation pathways are part of the Parkinson’s disease pathologic process.”