Israeli study probes a key factor in diagnosing Parkinson’s early: Constipation

A new study by Israeli researchers could constitute a step toward diagnosing Parkinson’s disease years earlier than is currently possible, potentially opening the door to successfully fighting the illness’s progression.

A team from the Hebrew University of Jerusalem isolated a key factor that is a common but not often discussed symptom of the degenerative disease: constipation.

While chronic constipation is a common problem as people age and is often not a sign that anything in particular is wrong, it has also been directly linked to Parkinson’s, sometimes appearing in patients up to 20 years before they are diagnosed with the disease.

Physicians currently lack a validated lab-based methodology for diagnosing Parkinson’s disease definitively, and it is diagnosed mainly based on motor symptoms that indicate the patient suffers from the disease, among them shaking, stiffness and difficulty with walking, balance and coordination.

By the time these symptoms are clearly visible, the brain has lost too many dopamine cells to make a recovery. Currently available treatments target the illness’s symptoms rather than reversing its progression.

Professor Joshua Goldberg of Hebrew University’s Department of Medical Neurobiology (Courtesy Joshua Goldberg)

But early diagnosis could be critical. Many promising treatments have failed in the trial stage, but according to Hebrew University’s Professor Joshua Goldberg, who led the recent study, this may not be because anything was inherently wrong with the treatment — but simply because the diagnosis was made too late for a potential cure to be helpful.

The Hebrew University research — published Wednesday in the journal Science Advances, and led by Professor Goldberg of the Department of Medical Neurobiology in collaboration with Professor Jochen Roeper of the Goethe University in Frankfurt, Germany, zeroed in on constipation as a potential early marker.

Parkinson’s has long been linked to the formation of tiny deposits of protein waste within brain cells called Lewy bodies, named after Dr. Friedrich Lewy who discovered them in 1912. It is not clear whether these protein deposits are a cause of the degenerative disease or a symptom of it. In fact, according to Goldberg, it could be a bit of both.

But the presence of Lewy bodies cannot be easily detected in living patients, and their prevalence in the brain has only been observed posthumously in those who’ve suffered from the disease. So on their own, they are not much use as a diagnostic tool.

An illustrative image of a patient with Parkinson’s disease (Obencem; iStock by Getty Images)

One of the first locations where Lewy bodies are found in the brain is an area that affects gastrointestinal activity — specifically the upper gastrointestinal tract.

Prof. Goldberg’s team sought to identify the specific underlying mechanism that connects the presence of Lewy bodies in the brain to constipation. Non-Parkinson’s constipation — the type that is not governed by brain issues — is usually centered in the large intestine rather than the upper gastrointestinal tract. So scientists hope identifying the mechanism responsible for constipation in the upper gastrointestinal tract will allow them to flag cases that are cause for concern.

In its study the research team found a way of detecting the way Lewy bodies impact the upper gastrointestinal system, using a specific protein, alpha-synuclein, that is known to be the main constituent of Lewy bodies.

The team over-expressed alpha-synuclein in mouse brain cells that modulate activity in the upper gastrointestinal tract.

“The result was that the over-expression of the protein caused these brain cells to shrink and their electrical activity to slow down,” the study found. The mice then indeed went on to develop constipation of the type that is associated with Parkinson’s.

A model for slowing down the digestive system following the expression of alpha-synuclein protein in the brainstem, as part of a study focusing on early diagnosis of Parkinson’s disease among those suffering from constipation. (J. Goldberg/J. Roeper)

“It is thus likely that this is the process that also occurs in humans in the early stages of Parkinson’s disease,” according to the study.

“As far as we know, this is the first time that anyone has described a causal chain of events connecting between how alpha-synuclein protein impacts brain cells and the early symptoms that we have long known predate this disease,” Goldberg said, touting the potential of the discovery.

“Consider a 55- to 60-year-old patient suffering from constipation. We may someday design a test based on the neural changes we discovered to determine whether there is a neural factor at play which could hint to Parkinson’s,” he said.

Goldberg stressed that early diagnosis would likely not be based merely on constipation and that a battery of tests would be used that taken together would indicate early presence of the disease.

This could then allow potential curative treatments to be administered before massive cell death develops in the brain, leaving the patient permanently and increasingly disabled.

While he admitted it was still hypothetical, he said: “One day in the future we are confident that we will be able to identify a variety of biomarkers — including physiological ones, like the one we propose — that will allow us to definitively diagnose the disease far earlier than we are currently able.”