Right now, Parkinson's disease is a clinical diagnosis. This means that you are diagnosed based on what symptoms you are presenting with, like a tremor. Studies show that when symptoms do arise, people with PD have already lost up to 60% of their dopamine.
Delayed diagnosis can lead to a quicker decline in function, but a faster diagnosis means treatment starts sooner. Diagnosing someone with PD can take 5-7 years which means too many important years without treatment have gone by. A recent study published in Nature Communications has found evidence of molecular changes in the brain and blood of people with PD who experience movement and cognitive changes related to Parkinson's. This finding is a really important step forward to developing new minimally invasive tests that can diagnose PD and track the course of the disease to ensure treatment is effective.
Before we go into the findings of this study, let's review a few key pieces of anatomy. There are two regions that are thought to be directly impacted by PD, the caudate and the putamen. When the caudate is impacted, cognitive changes are thought to occur. When the putamen is impacted, motor changes are though to occur. We still do not understand the molecular mechanisms underlying these changes.
Researchers of this study used brain samples from 35 people who died with Parkinson’s and 40 people who died without any neurological issues. They looked for changes in RNA (a molecule essential for various biological processes) and were able to identify thousands of RNAs in those with PD that differed from those who did not have the disease.
RNA changes were linked to the function of the part of our nerves that allow nerves to communicate to each other (synapse). Researchers found decreases in RNAs involved in dopamine neuron dysfunction and death, an increase in RNAs involved in inflammation and immune hyper-activation, and an increase in RNAs involved in stress response.
Researchers accessed samples from the Parkinson’s Progression Markers Initiative (PPMI). PPMI collects blood from people who do and do not have Parkinson’s. Researchers found that the RNA levels in the brain were altered in the same direction in the blood.
The researchers found 57 RNAs in the caudate that were significantly altered in donors that had been diagnosed with Parkinson’s disease dementia. When researchers looked at the differences in RNAs in the blood of people with PD vs. healthy controls, they found a few RNAs that were altered in people with PD.
The researchers found 18 RNAs in the putamen that were significantly altered in donors who experienced levodopa-induced dyskinesia. When researchers looked at differences in RNAs in the blood of people with PD vs. healthy controls, they found no significant differences.
The researchers found that those who were diagnosed earlier (before the age of 55) showed fewer molecular changes than those who were diagnosed later. Similar results were found in the blood.
Big Take Aways
People with Parkinson’s have unique changes in RNA molecules in brain. These changes occur in regions that rely on dopamine for regulating motivation, memory, cognitive and motor functions.
In people with PD there was shown to have similar RNA changes in blood samples.
Disease symptoms and features were associated with certain patterns of DNA changes.
Currently, there are no noninvasive tests to track molecular changes in the brain for people with PD. The results of this study highlights the real possibility to future noninvasive tests to be created! More research needs to be conducted before these findings can be used clinically.