Scientists have identified the subtype of brain cells that die in Parkinson's disease

In a groundbreaking new study published in the journal Nature on Thursday, researchers have compared the brain cells of patients who had died from either Parkinson's disease or dementia to people unaffected by the disorders and found which brain cells are responsible for both conditions.

The resulting identified cells can now be pinpointed and targeted by new research seeking to hopefully one day prevent and treat both the disorders.

22,000 brain cells examined

Neurobiologists Tushar Kamath and Abdulraouf Abdulraouf examined roughly 22,000 brain cells derived from human brain tissue samples of 10 patients who died from either Parkinson's disease or dementia with Lewy bodies and eight people unaffected by the illnesses.

Through this process, the team was able to isolate 10 distinct subtypes of dopamine-producing neurons in the substantia nigra, one of which stood out as largely missing in the brains of people with Parkinson's disease. They further discovered that the molecular processes linked to cell death in other neurodegenerative diseases were exaggerated in this same group of dopaminergic neurons.

From this analysis, they concluded that known genetic risk factors for Parkinson's disease might be acting upon "the most vulnerable neurons that influence their survival."

The study, however, does not have a sufficient amount of subjects to be conclusive. It can still, however, serve in further research on the two conditions.

Recreating vulnerable cells

Researchers can recreate these vulnerable cells in a lab to further study them and their influence on the human body. This new process could enable scientists to examine the genetic drivers of the diseases, evaluate potential future drug candidates, and even explore the possibility of regenerative treatments.

In addition, further studies that combine the current results with existing imaging data, tissue pathology studies, and genomic analyses can provide more answers about these two debilitating diseases. This begs the question: how close are we to finally developing therapeutic treatments for two conditions that plague so many people?

Abstract: 

The loss of dopamine (DA) neurons within the substantia nigra pars compacta (SNpc) is a defining pathological hallmark of Parkinson’s disease (PD). Nevertheless, the molecular features associated with DA neuron vulnerability have not yet been fully identified. Here, we developed a protocol to enrich and transcriptionally profile DA neurons from patients with PD and matched controls, sampling a total of 387,483 nuclei, including 22,048 DA neuron profiles. We identified ten populations and spatially localized each within the SNpc using Slide-seq. A single subtype, marked by the expression of the gene AGTR1 and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets of TP53 and NR2F2, nominating molecular processes associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.