Group 1

Metabolic Effects in Tauopathies

Understanding the molecular mechanisms underlying brain aging and neurodegenerative diseases remains a major challenge in the context of increasing life expectancy. The balance between healthy aging and pathological aging depends on multiple factors, and the early stages of this imbalance are key to understanding the molecular basis of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, in order to develop new diagnostics and treatments.

The team's strategy is to:

(1) Model neurodegenerative diseases and create innovative models by inducing pathology through gene transfer or the induction of inflammation, thereby enhancing the potential of the marmoset model, a natural model of age-related amyloidosis. The team has a longstanding commitment to better characterizing the aging marmoset. Our studies employ various approaches, including genetics, transcriptomics, viral transgenesis, histology, microfluidics, and more—all the way to brain magnetic resonance imaging (MRI) and behavioral and cognitive studies. Finally, we develop various cellular models (fibroblasts, neurons, etc.) from biopsies, which we use to explore new molecular signaling pathways or test new therapeutic targets.

(2) Identify potential biomarkers to address the pathological heterogeneity of neurodegenerative diseases by focusing on the Reg-1α protein, using a multidisciplinary approach ranging from cellular studies to in vivo models (zebrafish, rodents, non-human primates). Reg-1α is an inflammatory protein found both aggregated in the brains of patients with Alzheimer’s disease and capable of stimulating the hyperphosphorylation of the Tau protein in models of tauopathies. Currently, we are dissecting the molecular mechanisms linking Reg-1α to the characteristic lesions of tauopathies, with a particular focus on the impact of metabolic or inflammatory risk factors in this interaction.

(3) Chronic kidney disease (CKD) is a global public health issue, and epidemiological data suggest that individuals at all stages of CKD are at higher risk of developing neuropsychiatric disorders, cognitive impairment, and dementia. We are developing a new research focus at the interface between basic and medical research, with the objective of (1) understanding the impact of risk factors such as chronic kidney disease on the onset and progression of neurodegenerative diseases and (2) investigating Reg-1α as a new biomarker at the kidney-brain interface in a pathological context.

(4) We are also developing an epidemiological research program aimed at better identifying the role of lifestyle and metabolic factors in the aging process of the human brain