Neurodegenerative Diseases: Tracking Alzheimer’s and Parkinson’s in the Gut

It is just a courtyard that separates Nantes University Hospital from the TENS lab. A courtyard that the teams of Pascal Derkinderen and Moustapha Cissé cross when their colleagues perform a colon biopsy, or to go meet with patients. Because the research conducted by the lab has a clinical purpose: to track the links between neurodegenerative diseases and the enteric nervous system in order to better understand whether gastrointestinal disorders can serve as early markers.

Un chercheur dépose un échantillon, à l’aide d’une pipette automatique, dans un appareil d'allure complexe, pour mesurer sa perméabilité.
Thibauld Oullier, at TENS (unit 1235 Inserm/Nantes Université) ©Inserm/François Guénet

In terms of Parkinson’s, it has been accepted since the 1980s that the same lesions can be found on both the digestive and central neurons in some patients. In 2003, German researcher Heiko Braak proposed a highly debated theory: what if the disease began in the digestive neurons before reaching the brain? In some Alzheimer’s patients, the presence of beta-amyloid peptide deposits in the intestines, a sign of the disease in the brain, raises questions. Is this an early marker in an area that is easier to observe? More than ever, gut-brain relationships are the focus of intensive research.

Laurène Leclair-Visonneau et Pascal Derkinderen

Laurène Leclair-Visonneau and Pascal Derkinderen are conducting the IBIM-Park study, which looks at the role of inflammation and changes in the intestinal epithelial barrier in Parkinson’s. They are looking to see if this inflammation could be an early marker of the disease.

The colon biopsies taken at Nantes University Hospital are the size of a grain of rice, and it is in them that the scientists are looking for characteristic lesions on enteric neurons. Their research is supported by France Parkinson and other, local, patient associations, which are highly involved in the research.

Un chercheur dépose un minuscule échantillon sur une lame de verre
chambres de Ussing

The biopsies are placed in Ussing chambers, which measure digestive permeability. In Parkinson’s patients, it is suggested that the gut is more permeable – a hypothesis that IBIM-Park is expected to confirm or refute.

The enteric nervous system has the advantage of being accessible by means of a simple biopsy. In these freezers, each box contains biopsies from some twenty people. It is planned to include 80 volunteers in IBIM-Park by the end of the year, including 20 controls. The other 60 volunteers have Parkinson’s disease at various stages of progression.

Un chercheur devant un congélateur ouvert tient une boite pleine de petits tubes.
Moustapha Cissé à son bureau.

Moustapha Cissé is working on Alzheimer’s disease and gastrointestinal dysfunction. The Inserm researcher is wondering about the potential production of beta-amyloid in the gut. In the brain, beta-amyloid plaques are one of the signs of Alzheimer’s disease.

Deux images : Sur la première, un chercheur installe des plaques en plastique pour former un labyrinthe. La seconde montre le labyrinthe, vu du dessus, avec une souris qui s'y déplace.

Thibauld Oullier, a research engineer in the laboratory, is installing an elevated plus-maze, which is used to study the behavior of mice for Cissé’s research. Two arms of the cross are open, and two are closed on the sides. The mice are subjected to accelerated aging to simulate neurodegenerative deterioration. The more the animals are affected by the disease, the more they will be disinhibited and venture into the two open arms.

Maxime Mahé devant un microscope.

Maxime Mahé, Inserm researcher, is producing intestinal organoids from human pluripotent stem cells – each « cluster » on the screen is an organoid. These « reduced models » are used to study enteric neuron dysfunction in the epithelial barrier. All of which will give the scientists a better understanding of their involvement in neurodegenerative diseases.

Pascal Derkinderen and Moustapha Cissé lead the Neurodegenerative diseases research conducted at the Enteric Nervous System in Gut and Brain Disorders unit (TENS – Unit 1235 Inserm/Nantes University) in Nantes.