Could stool samples indicate who may develop Parkinson's?
- Researchers have investigated whether stool samples could be used to detect Parkinson’s disease before symptoms have settled in.
- They found that stool samples may be able to identify a condition that is an early indicator of Parkinson’s disease.
- They noted that further studies are needed to confirm their results.
Parkinson’s disease is a chronic, neurodegenerative condition. Symptoms include movement issues, cognitive impairment, and sensory disturbances.
In 2019, there were around 8.5 million individuals globally with the condition. According to the World Health Organization (WHO), the prevalence of Parkinson’s disease has doubled in the last 25 years.
Alpha-synuclein is a protein that plays a key role in neuronal function. Studies show that in synucleinopathies — conditions like Parkinson’s disease, Lewy body dementia, and multiple system atrophy, which is a form of dysautonomia — alpha-synuclein misfolds and forms aggregates, reducing neuronal function.
One study has also shown that 73.5% of people with isolated rapid eye movement sleep behavior disorder (iRBD) develop Parkinson’s disease, Lewy body dementia, or multiple system atrophy within 12 years.
iRBD is characterized by dream reenactment behaviors, such as kicking or punching in one’s sleep, and having vivid or violent dreams. Individuals with this condition also have high amounts of alpha-synuclein aggregates in the central and peripheral nervous systems.
Developing noninvasive ways to detect alpha-synuclein levels could help researchers monitor Parkinson’s disease risk and progression.
Recently, researchers set out to detect whether alpha-synuclein levels in the stool could predict Parkinson’s disease onset.
They found that patients with iRBD, but not healthy patients or those with Parkinson’s disease, had elevated levels of alpha-synuclein aggregates.
Their findings suggest that stool samples could aid in diagnosing conditions involving alpha-synuclein aggregates.
The study was published in npj Parkinson’s Disease.
What the study found
For the study, the researchers collected stool samples from:
- 94 participants with Parkinson’s disease
- 72 participants with iRBD
- 51 healthy controls.
The researchers then analyzed the stool samples for alpha-synuclein levels.
They found that individuals with iRBD with a high risk of developing conditions like Parkinson’s disease had significantly higher levels of alpha-synuclein aggregates than healthy controls and Parkinson’s disease patients.
From alpha-synuclein levels from still alone, the researchers were able to distinguish 76.4% of people with iRBD from healthy controls.
They noted, however, that they were unable to discriminate between Parkinson’s disease patients and controls from alpha-synuclein levels.
Alpha-synuclein and Parkinson’s disease
Longitudinal studies show that Parkinson’s disease patients have increased levels of aggregated alpha-synuclein in their cerebral spinal fluid as their condition advances.
The researchers noted that their stool sample results may have yielded different results for multiple reasons.
Firstly, they write that they did not characterize different kinds of Parkinson’s disease in their cohort. While 70% of Parkinson’s disease mechanisms originate in the central nervous system, around 30% originate in the intestinal nervous system, known as the enteric nervous system.
Distinguishing between types of Parkinson’s disease may have yielded different results.
They also caution that more alpha-synuclein might be excreted in stool prior to Parkinson’s disease onset, and less in advanced stages.
The researchers note that longitudinally collected stool samples for iRBD and Parkinson’s disease patients need to be assessed to understand the dynamics of alpha-synuclein aggregates.
“There are several limitations in the use of this biomarker,” Dr. Pratima Dibba, board-certified gastroenterologist at the Medical Offices of Manhattan, not involved in the study, told Medical News Today.
“Greater concentrations of alpha-synuclein aggregates in patients with iRBD does not distinguish what type of synucleinopathy a patient can develop, whether it is Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” she added.
Dr. Dibba also cautioned that different enzymes present in human stool may also alter the test results.
“It is important to note that components of stool, such as proteases, may distort the measured values of alpha-synuclein aggregates in the stool. Additionally, this biomarker was noted by investigators to have limited sensitivity and specificity. Interestingly, it was noted to be elevated in some control subjects, which may limit its positive predictive value,” she told us.
“The investigators also indicated that the method used to detect the aggregates, called surface-based fluorescence intensity distribution analysis (sFIDA) assay, does not distinguish between aggregates that are harmless to neurons versus those that are harmful to neurons,” Dr. Dibba further explained.
“Currently, our findings cannot be used to diagnose individual patients,” Prof. Erdem Gültekin Tamgüney from Heinrich Heine University Düsseldorf (HHU) in Germany, lead author of the study, emphasized for MNT.
“However, our findings could possibly be used to monitor the effect of a treatment during clinical studies. For example, should a treatment with a drug reduce alpha-synuclein aggregate levels in stool over time, it could indicate that the treatment is having an effect,” he noted.
MNT also asked Dr. Erin Furr Stimming, a neurology professor,and movement disorders specialist at the McGovern Medical School at UTHealth Houston, not involved in the study, about what these findings may mean for diagnosing Parkinson’s disease.
“With further study and refinement of the detection of alpha-synuclein aggregates stool, this method could potentially serve as a noninvasive tool to detect Parkinson’s disease many years prior to a clinical diagnosis. Earlier detection then allows for earlier intervention [once] an effective disease-modifying therapy is identified.”
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