Project Objectives

Researchers will screen both individual pollutants and mixtures—especially those that persist in the environment (persistent organic pollutants – POPs) or are newly linked to brain health, using in vitro models related to Alzheimer’s disease, the blood-brain barrier, and brain toxicity.

The goal is to find pollutants that disrupt brain-related processes and may trigger or worsen Alzheimer’s disease. These selected pollutants will then be studied further in human samples (like blood and hair) and examined for links to brain ageing and Alzheimer’s disease in both people (Objective #2) and pre-clinical models (Objective #3).

Expected Results

A list of pollutants (alone or in mixtures) that:

1. Speed up the formation of amyloid-β fibrils (a key marker of Alzheimer’s disease).
2. Increase brain cell toxicity (making nerve cells more likely to be damaged or die).
3. Disrupt the blood-brain barrier (weakening the brain’s natural defence system).

We will examine whether certain pollutants are more common in older adults who later develop Alzheimer’s disease, compared to those who don’t. We’ll also look at general dementia, memory decline, and brain scans as early signs of Alzheimer’s disease.

To do this, we’ll measure pollutant levels in blood and hair samples from participants in four European studies that track environmental health and brain ageing. These include both known pollutants (from Objective #1) and newer chemical markers.

The results will then be tested further in lab models (Objective #3 and Objective #4) to better understand how these pollutants might affect the brain.

Expected Results

By combining population studies with advanced chemical analysis of hair and blood samples, researchers will:

1. Identify early signs of pollutant exposure in people who later develop Alzheimer’s disease, even before symptoms appear.
2. Find pollutant patterns that can act as early warning signs or risk factors for developing Alzheimer’s disease.

The most harmful pollutants found in lab tests (Objective #1) and human studies (Objective #2) will be tested in advanced Alzheimer’s disease models:

• Human brain cell cultures made from stem cells of Alzheimer’s disease patients.
• Two types of genetically modified mice that mimic Alzheimer’s disease.

These models will help our researchers:

1. Understand how pollutants affect the brain at the molecular level, including changes to known Alzheimer’s disease markers or the appearance of new ones.
2. See how pollutants worsen memory and thinking problems in the early stages of the disease.

Findings from these models will be compared with human data (from Objective #2) to better understand their impact on brain ageing.

Expected Results

1. In lab models (cells and animals), researchers will uncover how pollutants, alone or in mixtures, trigger brain damage linked to Alzheimer’s disease (Objective #1).
2. In human studies, they will find correlations and causal associations between pollutant exposure and dementia risk (Objective #2).

Some brain diseases, like Alzheimer’s disease, may begin with subtle damage during early brain development caused by chemical exposure. This idea is known as the neurodevelopmental hypothesis.

Researchers aim to discover how early exposure to environmental pollutants might increase the risk of developing Alzheimer’s disease later in life. They will use:

• 3D brain models (organoids) made from healthy human stem cells to mimic early brain development.
• Animal models where mother and offspring are exposed to pollutants to study long-term effects.

These models will help show whether early-life exposure makes the brain more vulnerable to Alzheimer’s disease as people age.

Expected Results

In the organoid models, we will observe how pollutants affect early brain development, such as:

• Problems in forming cortical layers.
• Issues with how brain cells move and develop.
• Changes in how brain cells are organised.

In the in vivo models, we will identify pollutants that:

• Cause early behavioural problems in young animals that may lead to Alzheimer’s disease-like symptoms in later life.
• Lead to Alzheimer’s disease-like brain changes and memory issues in older animals.

These findings could help predict who is at risk and support early diagnosis of neurodegenerative diseases in people exposed to harmful pollutants.

To disseminate and utilise the project’s results by:

• Creating prevention strategies and policy recommendations for areas with a high pollution risk.
• Offering training and education programs for the public, researchers, industry, and healthcare professionals.
• Providing recommendations and evidence-based guidance for policymakers.
• Promoting collaboration and knowledge-sharing with other projects to boost impact and develop joint actions, including with the ExpoHealthNet cluster.

Expected Results

Sharing knowledge and raising awareness through:

1. Public outreach – website, social media, and videos to inform the public.
2. Education & training – webinars, events, and training sessions for healthcare professionals and the public.
3. Policy impact – new, evidence-based guidelines for decision-makers.
4. Scientific contribution – research findings published in peer-reviewed journals.

The research is supported by additional work packages for management (Inserm A and Inserm Transfert) and cluster activities.