Indication of Parkinson’s preform in stool sample
The so-called isolated REM sleep behavior disorder is a disease that can indicate Parkinson’s disease well in advance. A research team led by Prof. Dr. Erdem Gültekin Tamgüney, a scientist at Forschungszentrum Jülich from the Helmholtz Research Field Information and Heinrich Heine University Düsseldorf (HHU), shows that an increased concentration of α-synuclein aggregates can be detected in the stool of affected individuals. In the journal “npj Parkinson’s disease”, which belongs to the NatureSpringer group, the team presents a detection method for these aggregates, which they developed together with the University Hospital Cologne and attyloid GmbH. (Source: Forschungszentrum Jülich – Press Releases)
There are two forms of Parkinson’s disease (PD for short). In 70 percent of cases, it originates in the central nervous system (CNS). In about 30 percent of those affected, the origin is in the nervous system of the intestine (“enteric nervous system”). The latter is referred to as “body-origin PD” (body-first PD for short). In this form, the characteristic deposits of aggregates of the body’s own α-synuclein protein form in the neurons in the intestinal area.
A preliminary form of body-first PD is the so-called isolated REM sleep behavior disorder (in short “iRBD”). It is expressed by partially complex movements during a specific sleep phase – REM sleep – provided that the patient has vivid and frightening dreams. These movements can lead to danger to self or others.
A research team led by Prof. Dr. Erdem Gültekin Tamgüney of the Institute for Biological Information Processes (IBI-7) of the Research Center Jülich from the Helmholtz Research Field Information and the Institute of Physical Biology at HHU now reports that they detect elevated levels of α-synuclein aggregates in stool samples from affected patients. To do so, they used a new surface-based fluorescence intensity distribution analysis (“sFIDA”) to detect and quantify individual particles of α-synuclein aggregates.
Prof. Tamgüney: “We were the first to detect α-synuclein aggregates in stool. Our results show significantly increased levels of α-synuclein aggregates in iRBD patients compared to healthy individuals or patients with Parkinson’s disease. These findings may lead to a non-invasive diagnostic tool for synucleinopathies that are still asymptomatic (“prodromal”) – including Parkinson’s disease. This could allow early initiation of therapies before symptoms appear.” More research is needed before the method can enter clinical practice. For example, why the level was lower in Parkinson’s patients is the subject of further investigation.
The study was conducted jointly by the Institute for Biological Information Processes – Structural Biochemistry (IBI-7) at Forschungszentrum Jülich, the Clinic and Polyclinic for Neurology at the University Hospital of Cologne (UKK) and the HHU and Jülich spin-off attyloid GmbH. HHU and UKK have established the biobank with stool samples from patients and control subjects. The research center and HHU developed the test procedure and performed the tests with the samples. The attyloid GmbH is a cooperation partner and wants to work on a commercial exploitation of the results. Here, it must be verified that the test procedure is safe and can be used in regular operation and thus receive approval.
Background
In body-first PD, the deposits of fibrils of the endogenous protein alpha-synuclein, which are characteristic of Parkinson’s disease, first form in neurons of the enteric nervous system, which supplies the gastrointestinal tract. From there, the aggregates then migrate prion-like to the CNS. “Prion-like” here means that an existing aggregate, like a seed of crystallization, causes individual alpha-synuclein proteins in their vicinity to also assemble into aggregates, causing them to spread further throughout the body.
The influence of events in the gastrointestinal tract on the brain is called the “gastrointestinal-brain axis”. The gastrointestinal tract is exposed to the environment. There is a possibility that contaminants ingested with food, such as chemicals, bacteria or viruses, could trigger the pathological formation of alpha-synuclein aggregates, either directly or through an interaction with the microbiome of the gastrointestinal tract.
Prof. Tamgüney’s group previously demonstrated that gastrointestinal infections increase the risk of PD (see Nerius et al, 2019 in Gut. DOI: 10.1136/gutjnl-2019-318822. Also, a Bonn-Düsseldorf research team led by Tamgüney was able to show in an animal model that orally administered α-synuclein fibrils can be taken up in the gastrointestinal tract and spread from there in a prion-like manner to the CNS, where they can trigger PD-like disease (see Lohmann et al, 2019 in Acta Neuropathologica, DOI: 10.1007/s00401-019-02037-5).
HHU/Arne Claussen, 13.02.2023
The original press release can be found at:
Hinweis auf Parkinson-Vorform in Stuhlprobe (only in german)
The original publication can be found at:
Originalpublikation: Anja Schaffrath, Sophia Schleyken, Aline Seger , Hannah Jergas, Pelin Özdüzenciler, Marlene Pils, Lara Blömeke, Anneliese Cousin, Johannes Willbold, Tuyen Bujnicki, Oliver Bannach, Gereon R. Fink, Dieter Willbold, Michael Sommerauer, Michael T. Barbe and Gültekin Tamgüney, Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool, npj Parkinson’s Disease (2023) 14. DOI: https://doi.org/10.1038/s41531-023-00458-4
Localization in the Helmholtz Research Field Information:
Helmholtz Research Field Information, Program 2: Natural, Artificial and Cognitive Information Processing, Topic 4: Molecular and Cellular Information Processing
Contact:
Prof. Dr. Erdem Gültekin Tamgüney
Institute of Biological Information Processing (IBI)
Structural Biochemistry (IBI-7)
Forschungszentrum Jülich
Phone: +49 2461/61-5070
E-Mail: e.tamgueney@fz-juelich.de
Anja Schaffrath
Institute of Biological Information Processing (IBI)
Structural Biochemistry (IBI-7)
Forschungszentrum Jülich
Phone: +49 2461/61-2117
E-Mail: a.schaffrath@fz-juelich.de
Prof. Dr. Dieter Willbold
Institute of Biological Information Processing (IBI)
Structural Biochemistry (IBI-7)
Forschungszentrum Jülich
Phone: +49 2461/61-2100
E-Mail: d.willbold@fz-juelich.de
