Personnels involved : David Blum, Anna Bogdanova, Luc Buée, Ming-Li Chou, Camille Degryse, Vincent Deramecourt, Marie Dubar, Eloïse Gilbert, Sophie Halliez, Vincent Huin, Brenda Lammens, Thibaut Nicod, Espérance Pastouret, Camille Lefebvre

 

In Alzheimer's disease and tauopathies, a disruption of neuroglial homeostasis appears to be predominant in the development of the pathology itself, but also in its cognitive consequences.

 

In this context, we seek not only to better understand how Tauopathy affects the interactions between astrocytes and neurons, but also how these dysfunctions contribute to the progression of Tauopathy.

To this end, we carry out and characterize primary neuron-astrocyte co-cultures in microfluidic devices in order to study precisely how the astrocytic dysfunctions observed in Alzheimer's disease affect synaptic transmission (collaboration with Alexis Bemelmans & Karine Cambon, MirCen, Fontenay-aux-Roses).

[Translate to English:] photo astrocyte

Primary astrocyte (here in green with the nucleus in blue) in the presence of neurites (here in white) forming synapses within a microfluidic cell culture chamber

 

While research has long focused on certain immune cells such as microglia and lymphocytes, our team has chosen to explore a still largely unknown area: the role of neutrophils and their extracellular traps (NETs). We are deciphering how these mechanisms are linked to tauopathy, influence pathological progression, and impact the neuroimmune and neuroinflammatory landscape. These studies are conducted by combining the study of innovative experimental models and the analysis of autopsy human tissues, paving the way for new and innovative therapeutic strategies (Guillaume Dorothée, CRSA, Paris).

 

photo neutrophil

Within the context of this research on the role of neuroglial and neuroimmune interactions in Alzheimer's disease and tauopathies, we are also interested in the impact of certain infections on the pathophysiological development associated with tau. Epidemiological and experimental data suggest, in particular, that certain infectious conditions responsible for chronic low-grade peripheral inflammation, such as periodontitis—a chronic inflammatory disease of periodontal tissues induced by bacterial dysbiosis and commonly referred to as "gum recession"—are associated with impaired cognitive performance and an increased risk of neurocognitive disorders.

 

Furthermore, the gut microbiota, via the gut-brain axis, is involved in modulating the systemic inflammatory response and neurobiological processes relevant to neurodegenerative diseases, including Tau pathology in experimental models. Although distinct, the periodontal and gut microbiotas may contribute to a shared systemic inflammatory context, potentially influencing certain neurobiological processes involved in cognitive decline.

Thus, we are exploring the associations between periodontal status, oral/periodontal and intestinal microbiota, inflammatory markers, and cognitive function in the early stages of cognitive decline, combining clinical, biological, and preclinical approaches. The objective is to better characterize the biological contexts associated with early cognitive vulnerability, from a translational perspective (Collaborations: Rodrigue Dessein, Lille University Hospital; Kathy Dujardin, team TREAT).

Furthermore, we are also interested in a common neurotropic pathogen that persists in the brain, Toxoplasma gondii (Tg), which could therefore influence the pathophysiological evolution in a context of Tauopathy.

 

We are particularly focused on identifying and deciphering the underlying mechanisms at the neuronal and neuro-immune level (Collaborations: Sabrina Marion, CIIL, Lille; Elsa Suberbielle & Nicolas Blanchard Infinity, Toulouse)

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