The specific subset of brain cells that die in Parkinson’s disease patients has been identified, thus solving one of the biggest mysteries surrounding the disease. Presenting their research in the journal Nature Neuroscience, the study authors say their findings could lead to the development of new treatments that target these vulnerable neurons.
The degradation of dopamine neurons within a brain region called the substantia nigra pars compacta (SNpc) is an important feature of Parkinson’s disease and other forms of dementia. Because dopamine helps regulate mood, cognition, and motor control, loss of these cells often leads to symptoms that include tremors, depression, and cognitive decline.
However, not all dopamine neurons in the SNpc are affected, and some die early in the disease, while others remain intact. To understand why this is the case, the study authors looked at a total of 22,048 brain cells from 10 deceased patients with Parkinson’s and dementia and eight people who died without any cognitive impairment.
After measuring gene expression patterns within these cells, they found that there are in fact 10 distinct subpopulations of dopaminergic neurons within the SNcp, distinguishable by their unique transcriptional profile. One of these clusters was located predominantly in the ventral, or lower, region of the SNcp, consistent with previously identified patterns of neuronal degeneration in dementia.
Sure enough, when the researchers looked at the brains of the latest study participants, they found that this group of neurons was largely missing in Parkinson’s and dementia sufferers. Further analysis of these cells revealed an upregulation of genes that are strongly involved in cell death processes, suggesting that these neurons may be the first to be damaged in individuals with neurodegenerative diseases.
The irrefutable proof was confirmed when the authors noted that this particular subset of neurons contained the highest expression of genes associated with the risk of developing Parkinson’s disease. Taken together, these observations seem to indicate that this group of neurons is particularly vulnerable to degeneration in people with genetic susceptibility to the disease, and that loss of these cells may be predominantly responsible for many of the symptoms associated with the disease.
The study authors therefore call for future research to focus specifically on this subpopulation of cells, suggesting that they may hold the key to treating Parkinson’s disease.