Parkinson’s disease is traditionally understood as a neurodegenerative disease that starts in the brain. While this might be true in some cases, growing evidence suggests that the disorder is actually two diseases, with one variant starting in the gut.
In a new study of brain imaging, the researchers found that in some Parkinson’s patients, nervous system damage begins and in the intestinal nervous system then travels to the brain.
In other patients, the disease appears to appear in the brain first.
“So far, many people have viewed the disease as relatively homogeneous and defined it using the classic movement disorders,” says neuroscientist Per Borghammer from Aarhus University in Denmark.
“At the same time, we were confused as to why there was such a big difference between the patients̵
While the new study is small – including just 37 people with Parkinson’s or classified as at risk, everyone between the ages of 50 and 85 – the researchers say their cohort is large enough to reveal highly significant differences using advanced imaging techniques like PET and MRI .
In the study, a significant number of participants also had a closely related REM sleep disorder, and the team found that this particular problem that causes people to achieve their dreams tends to signal the body’s own progression of Parkinson’s.
The researchers suspect that this is likely because the pathology of the disease first migrates from the intestines to a part of the brain closely related to REM sleep before moving on to the substantia nigra, from which Parkinson’s disease des first brain originates.
The study used REM sleep disorder to determine who might be at risk for Parkinson’s later, and suggested that this might be a sign of neurodegeneration ahead. Brain scans and other assessments of body health and nerve function created profiles that clearly set out two different biological signals.
This implies that there can actually be two variants of the disease, each of which begins in different parts of the body and then progresses in slightly different ways.
The authors name the two different manifestations Body-First-Parkinson and Brain-First-Parkinson.
“Previous studies have shown that there could be more than one type of Parkinson’s disease, but it was only clearly demonstrated in this study, which was specifically designed to answer this question,” says Borghammer.
“We now have knowledge that offers hope for better, more targeted treatment for people with future Parkinson’s disease.”
The gut was first associated with Parkinson’s disease nearly two centuries ago. Today constipation is one of the most common symptoms of the disease, and yet it was only in 2003 that the neuroanatomist Heiko Braak suggested an intestinal origin for Parkinson’s after a thorough examination of the corpses.
Since then, further studies have produced mixed opinions. While some animal studies suggest that there is a passage for Parkinson’s biomarkers to spread from the gut to the brain, human autopsy studies suggest that these are only a minority of cases.
In a study with over 600 bodies, the researchers did not find a single case of Parkinson’s. It has all been found to come from the brain.
But that doesn’t mean that the gut nervous system known as the enteric nervous system isn’t involved. The gastrointestinal tract is huge, and some researchers argue that it would take many hundreds of slides to rule out localized bowel pathology “with any degree of certainty”.
It has proven difficult to find evidence of bowel-first cases where similar progress has been made. However, the new study suggests that there may be a middle ground between the mixed results.
The authors predict from the current trajectories that all patients, regardless of how their Parkinson’s disease started, will potentially develop severe damage to their sympathetic nervous system.
This means that both variants look very similar – be it the dopamine system in your brain, which starts to degenerate first, or the peripheral nervous system.
Knowing about these two variants could help us identify the pre-stages of Parkinson’s much earlier – at least for the body-first variant.
“The next step is to investigate whether, for example, Parkinson’s disease can be treated with the body first, by treating the intestines with a fecal transplant or in some other way that affects the microbiome,” says Borghammer.
If this body’s own origin of Parkinson’s actually exists, we may be able to stop the disease before it progresses to the brain. Once it’s in our heads, it’s much harder to control.
Unfortunately, by the time symptoms from the first variant of the brain show up, cognitive degeneration is already quite advanced. By then, Borghammer says they have already lost more than half their dopamine system, which means slowing the disease down will be much more difficult.
The study was published in brain.