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High levels of ?-synuclein protein aggregates are present in the brain and enteric or intestinal nervous system of patients with Parkinson's disease. 
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Preliminary Form of Parkinson’s Indicator in Stool Sample

Isolated REM sleep behavior and gut-brain axis may also help study Parkinson’s disease

Heinrich Heine University Düsseldorf
Published:Feb 16, 2023
|3 min read
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The isolated REM-sleep behavior disorder (iBRD) is a condition that can provide an indication of Parkinson’s disease well in advance. A research team headed by Erdem Gültekin Tamgüney, PhD, professor at the Heinrich Heine University Düsseldorf (HHU) has shown that a greater concentration of α-synuclein aggregates can be detected in the stool samples of sufferers. 

In the scientific journal npj Parkinson’s Disease, published by the NatureSpringer group, they present a method for detecting these aggregates, which they have developed in collaboration with the University Hospital Cologne, Jülich Research Center (FZJ), and the company, attyloid GmbH.

Forms of Parkinson’s disease: PD and body-first PD

There are two forms of Parkinson’s disease (PD). In 70 percent of cases, it originates in the central nervous system. However, in around 30 percent of cases it originates in the nervous system of the intestine (enteric nervous system). The latter form is referred to as body-first Parkinson’s disease (body-first PD) and the characteristic deposits of aggregates of the body’s own α-synuclein protein are formed in the neurons in the intestine.

A preliminary form of body-first PD is the so-called isolated REM-sleep behavior disorder (iBRD). It causes complex movements during a specific phase of sleep—REM sleep—as the patient experiences vivid and disturbing dreams. These movements can endanger the sufferer themselves or others.

A research team headed by Tamgüney from the Institute of Physical Biology at HHU reports that it is possible to detect an elevated level of α-synuclein aggregates in the stool samples of patients. To achieve this, the team used a new surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify individual particles of α-synuclein aggregates.

“We are the first to prove the presence of α-synuclein aggregates in stool samples. Our results show a significantly higher level of α-synuclein aggregates in iRBD patients compared with healthy individuals or patients with Parkinson’s. These findings could lead to a noninvasive diagnostic tool for prodromal synucleinopathies—including Parkinson’s—which could in turn enable therapies to be initiated at an early stage before symptoms occur,” said Tamgüney. However, more research is required before the process can find its way into clinical practice, for example, an investigation into why the level is lower in Parkinson’s patients. 

The study was conducted in collaboration with the Institute of Biological Information Processing–Structural Biochemistry (IBI-7) at Jülich Research Center (FZJ), the Department of Neurology at the University Hospital Cologne, and the HHU/FZJ spin-off attyloid GmbH. HHU worked with the University Hospital Cologne to establish a biobank with stool samples from patients and control subjects, and with FZJ to develop the test procedure and conduct the tests on the samples. attyloid GmbH is a cooperation partner and is working towards the commercial exploitation of the results. It is necessary to verify that the test procedure is safe and can be used in normal operations in order to gain a license. 

PD and the gut-brain axis

In body-first PD, the deposits of the body's own α-synuclein protein fibrils, are first formed in the neurons of the enteric nervous system, which serves the gastrointestinal tract. The aggregates then spread to the central nervous system in a way similar to prions, i.e., an existing aggregate combines individual α-synuclein proteins in its vicinity into further aggregates in a nucleation process; these aggregates then spread further through the body.

The influence of what happens in the gastrointestinal tract on the brain is referred to as the gut-brain axis. The gastrointestinal tract is exposed to the environment and it is possible that harmful substances such as chemicals, bacteria, or viruses ingested directly with food or via interaction with the microbiome of the gastrointestinal tract may trigger the pathological formation of α-synuclein aggregates.

The working group headed by Tamgüney has already proven that gastrointestinal infections are associated with an increased risk of PD. A Bonn- and Düsseldorf-based research team headed by Tamgüney has also shown in an animal model that α-synuclein fibrils administered orally are absorbed in the gastrointestinal tract and spread to the central nervous system in a way similar to prions, and can then trigger a PD-like illness there.

- This press release was originally published on the Heinrich Heine University Düsseldorf website