EXPOSIGNALZ : A new large translational research program on pollutant mixtures in brain aging and Alzheimer’s disease

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Through interdisciplinary approaches, integrating experimental and epidemiological studies,
the EXPOSIGNALZ project aims to delineate the impact of a selection of environmental pollutants
on brain health throughout life and their role in dementia, especially Alzheimer’s disease (AD),
representing about 70% of dementia cases

EXPOSIGNALZ is a new Horizon Europe project funded under the ‘Horizon and Health’ 2024 call, coordinated by V. Perrier of the Montpellier Neuroscience Institute (Inserm) and in which Cecilia Samiéri of the BPH ELEANOR team is a partner.

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Do the various pollutants that surround us play a role in the development of dementia, specifically in Alzheimer’s patients?

How do these substances interact with our bodies and brains?

What are the consequences depending on the time window of exposure?

These are all questions that the EXPOSIGNALZ project is trying to answer using an interdisciplinary approach.

The impact of certain combinations of environmental pollutants will be evaluated on preclinical models of Alzheimer’s disease.
Research will be carried out to identify combinations of pollutants associated with the risk of developing Alzheimer’s disease or clinical and biological alterations.

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Cécilia Samieri was funded 1.4 M€ with this program to lead with her group in ELEANOR the human research part dedicated to discovering novel pollutant mixtures associated with brain aging.

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As director of research at Inserm, specialising in the epidemiology of brain ageing, Cecilia Samieri’s work aims to understand the role of environmental factors in the apparition of age-related brain diseases, in particular dementia and its main form, Alzheimer’s disease.

Cecilia and her ELEANOR group at the BPH are using molecular epidemiology and in-depth phenotyping of the brain to identify the factors and mechanisms that, early in life, enable the brain to adapt to ageing or, conversely, to lead to the dementia of Alzheimer’s disease. The aim of these studies is to put in place early prevention strategies likely to delay or avoid the disease.

The ultimate aim is to reduce the burden of this disease on society

To characterise the biological fingerprints of pollutants associated with cerebral ageing and Alzheimer’s disease in several biological matrices, and to decode the mechanisms of action of the pollutant signatures identified, from neurodevelopment to neurodegeneration, in various preclinical models, they will be based on several French/European cohorts, including two cohorts set up at the BPH:

- - - The Three-city (3C) studies involve 9,294 participants from 3 different cities (Bordeaux, Dijon and Montpellier) to prevent dementia and determine the link between vascular disease and Alzheimer’s disease.

- - - Biobank and brain health in Bordeaux (Bcube) is working to identify potential solutions for the early prevention of Alzheimer’s disease, by studying the exposome of brain ageing in its early stages, with a particular focus on nutrition and lifestyle in young seniors aged 55 and over.