Parkinson’s disrupts key brain connections, PET scan study finds
Insights could help researchers zero in on biological mechanisms driving disease
- Parkinson's disease disrupts the normal connection between dopamine neurons and nerve cell synapses in key brain regions.
- PET scans reveal this distinct loss of association in the striatum and substantia nigra.
- These findings offer insights into disease progression and potential early diagnostic markers.
People with Parkinson’s disease exhibit an interplay between the loss of dopamine-producing neurons and overall nerve cell connections, or synapses, in two key brain regions that is distinct from that seen in individuals without the disease, according to a recent study.
Researchers demonstrated that in Parkinson’s, the association between dopaminergic neurons and synaptic density in the striatum was lost, and that synaptic density in the substantia nigra was significantly correlated with the number of dopaminergic neurons in the striatum. The substantia nigra and the striatum are brain regions involved in motor control and are among those most affected in Parkinson’s.
“Understanding how dopamine loss and the breakdown of brain connections overlap, or don’t, over time could shed light on why Parkinson’s disease progresses the way it does,” Tommaso Volpi, MD, PhD, a postdoctoral associate in the department of radiology and biomedical imaging at Yale School of Medicine and co-author of the study, said in a university news story. “These insights could also help researchers zero in on the biological mechanisms driving the disease, which are still somewhat elusive.”
The study, “Measuring Dopamine Transporter Availability and Synaptic Density in Parkinson’s Disease: A Dual-Tracer Positron Emission Tomography Imaging Study,” was published in Movement Disorders.
Researchers measure key markers in Parkinson’s patients’ brains
Parkinson’s disease is caused by the progressive loss of dopaminergic neurons, the nerve cells responsible for producing dopamine, a key signaling molecule for motor control. These neurons are normally found in a part of the brain called the substantia nigra, and communicate with neurons in the striatum, another brain region, through the nigrostriatal pathway.
By the time motor symptoms appear, including tremor, rigidity, and slowed movements, patients have already lost about half of the affected neurons. This highlights “the importance of advanced imaging methods for an early and reliable diagnosis,” the researchers wrote.
In this study, a team of researchers at Yale University employed positron emission tomography (PET) using radioactive tracers to measure two markers in patients’ brains: dopamine transporters, a marker of dopaminergic neurons, and synaptic density, a measure of the number of connections between nerve cells, or synapses.
The study included 30 patients with Parkinson’s disease and 13 healthy volunteers, who underwent two separate PET scans to assess dopamine transporters and synaptic density. Patients had a mean age of 65.8 years and a disease duration of 5.9 years, and most were men (60%). They were older than healthy participants (57.6 years) and had a shorter time between PET scans (90 days vs. 377 days).
In healthy brains, we saw a strong correlation between dopamine neuron density and synaptic density. In Parkinson’s disease, that relationship deteriorated, and that to me is the heart of our study.
When comparing the two measurements in the substantia nigra and striatum, the researchers observed that in healthy participants, the number of dopamine neurons in a region of the striatum called the caudate significantly correlated with synaptic density in all striatal regions (caudate, putamen, and ventral striatum).
This connection was lost in people with Parkinson’s, where striatum dopaminergic neuronal loss was more prominent than synaptic loss. These changes were already apparent in early stages of the disease and became more pronounced in later stages.
In patients, a correlation was observed between dopaminergic neuron density and synaptic density in the substantia nigra, as well as between synaptic density in the substantia nigra and the number of dopaminergic neurons in the striatum.
“In healthy brains, we saw a strong correlation between dopamine neuron density and synaptic density,” said David Matuskey, MD, professor at Yale and senior author of the study. “In Parkinson’s disease, that relationship deteriorated, and that to me is the heart of our study.”
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