Human populations are impregnated by various types of chemical pollutants reported as “hazardous waste” present in the environment. Certain pollutants have adverse effects on brain, but the underlying mechanisms and time-window exposures are still unknown, as well as their contribution on dementia, the 7th leading cause of death. 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. Through interdisciplinary approaches, integrating experimental and epidemiological studies, our objectives are to: 1) Identify environmental pollutants likely to have neurotoxic effects and pro-amyloidogenic properties predictive of a neurodegenerative trajectory related to AD using in vitro screening models; 2) Characterize pollutant signatures associated with brain aging and AD in biological matrices of 4 European population-based cohorts of various age groups; 3) Understand the mechanisms of action of pollutants identified in the in vitro screenings and those found in biological signatures, using AD-iPSC and AD preclinical models; 4) Explore the impact of pollutants on early neurodevelopment as a factor of susceptibility for later neurodegenerative diseases using brain organoids and gestational contamination models and 5) Disseminate knowledge to policy makers, to the relevant stakeholders and general public in order to define guidelines for disease prevention and take actions for population’s health. The project, which aims to identify chemical pollutants as new risk factors for dementia as well as new pollutant-associated biomarkers, could contribute to: (i) reduce or delay the incidence of AD, and thus reduce the economic and social burden; and (ii) allow an earlier diagnosis of AD combined with new disease modifying treatments to delay the entrance of patients in the more severe stages of the pathology.

The Innovative Manufacturing and Construction Research Centre (IMCRC) will undertake a wide variety of work in the Manufacturing, Construction and product design areas. The work will be contained within 5 programmes:1. Transforming Organisations / Providing individuals, organisations, sectors and regions with the dynamic and innovative capability to thrive in a complex and uncertain future2. High Value Assets / Delivering tools, techniques and designs to maximise the through-life value of high capital cost, long life physical assets3. Healthy & Secure Future / Meeting the growing need for products & environments that promote health, safety and security4. Next Generation Technologies / The future materials, processes, production and information systems to deliver products to the customer5. Customised Products / The design and optimisation techniques to deliver customer specific products.Academics within the Loughborough IMCRC have an internationally leading track record in these areas and a history of strong collaborations to gear IMCRC capabilities with the complementary strengths of external groups.Innovative activities are increasingly distributed across the value chain. The impressive scope of the IMCRC helps us mirror this industrial reality, and enhances knowledge transfer. This advantage of the size and diversity of activities within the IMCRC compared with other smaller UK centres gives the Loughborough IMCRC a leading role in this technology and value chain integration area. Loughborough IMCRC as by far the biggest IMRC (in terms of number of academics, researchers and in funding) can take a more holistic approach and has the skills to generate, identify and integrate expertise from elsewhere as required. Therefore, a large proportion of the Centre funding (approximately 50%) will be allocated to Integration projects or Grand Challenges that cover a spectrum of expertise.The Centre covers a wide range of activities from Concept to Creation.The activities of the Centre will take place in collaboration with the world's best researchers in the UK and abroad. The academics within the Centre will be organised into 3 Research Units so that they can be co-ordinated effectively and can cooperate on Programmes.