Research Projects

We pioneered an initially highly controversial connection between DNA damage and (accelerated) aging. In the previous ERC grant ‘DamAge’ we reached the stage that (segmental) aging in DNA repair-deficient mice can be largely controlled. The severity of the repair defect determines the rate of segmental aging; the repair pathways affected influence...

Alzheimer’s disease (AD) affects worldwide ~50 million people. Preclinical research relies mainly on transgenic mouse models overexpressing mutant human proteins that are altered in <5% of AD cases (e.g. β-amyloid and tau), however, despite prominent protein aggregates, they fail to show the dramatic neurodegeneration and cognitive decline of patients, indicating that plaques and tangles may not be the only requirement for AD. Age is the most determining factor in AD, but is poorly represented in current AD models.
Generating bona fide mouse models for various human DNA repair syndromes we have disclosed a very strong connection between DNA damage, repair and aging including dramatic neurodegeneration. Within the context of ERC-DamAge we discovered striking parallels in neurodegeneration, progressive cognitive decline and genome-wide expression profiles of repair-deficient Ercc1Δ/- mice and human AD. The similarities in expression profiles are an order of magnitude higher than current AD mouse models. We discovered that nutritional interventions can spectacularly delay neurodegeneration, opening realistic perspectives for combating AD and other neurodegenerative disorders. The primary goal of this application is to complete the characterization of the mouse mutants as a valid model for AD by a detailed quantitative comparison of all RNA classes of relevant brain compartments of Ercc1Δ/- mutants and AD patients. This not only provides the final PoC, but also an unparalleled resource for pathway analysis, target identification and biomarkers for monitoring disease progression and effects of any intervention. This application will be instrumental to facilitate transition to a valid AD model for pharmaceutical companies enabling development of effective medication for prevention and/or therapy. This proposal addresses a huge unmet medical need worldwide, which seriously affects QoL, challenges health care systems, and offers unprecedented socio-economical opportunities.

As the use of nanoparticles becomes more prevalent, it is clear that human exposure will inevitably increase. Considering the rapidly ageing European population and the resulting increase in the incidence of neurodegenerative diseases, there is an urgent need to address the risk presented by nanoparticles towards neurodegenerative diseases. It is...

Neurodegenerative diseases are the top 3 leading causes of death and are viewed now as systemic diseases. Adaptive immunity including a T-cell response in the central nervous system (CNS) likely contributes to disease pathogenesis. How T cells are primed and recruited to CNS is largely unexplored, due to the complexity of the process and lack of...

There is an urgent medical need for efficient diagnostics for Alzheimer’s disease and related tauopathies, as well as disease modifying treatments, due to the heavy burden of the disease on patients, families and society. To address this public health issue, TAME R&I training network gathers leading academic and industrial experts in tau research...

CNS disorders, e.g. brain cancer and Alzheimers disease, are the most common, debilitating, and underserved diseases. CNS drugs have historically suffered from considerably lower success rates during development than those for non-CNS indications. One of the major reasons is the presence of CNS barriers, including the blood-brain (BBB) and blood...

Alzheimer’s disease (AD) is a global health burden. There are currently no treatments that prevent AD or modify the course of the disease. Recent work has identified several subtypes of Alzheimer’s disease that become apparent once clinical symptoms appear. These subtypes can guide improved treatment and care decisions. Here we aim to predict which...

The AAL project eWare “Early Warning (by lifestyle monitoring) Accompanies Robotics Excellence” is focused on improving the lifestyle of people with dementia and their caregivers considering the extreme impact of this disease in the world. Caring for a person with dementia (PwD) can be a significant personal and emotional challenge for informal...

The Project eBrain-Health will deliver a distributed research platform for modeling and simulating complex neurobiological phenomena of human brain function and dysfunction in a data protection compliant environment. It will provide thousands of multilevel virtual brains from patients and healthy human controls for research and innovation. Brain...

The four-year MICRO-THERAPY is a fully integrated interdisciplinary proposal which will develop a new area of competence in the three partners, Liverpool John Moores University, University of Rennes1 and ManRos Therapeutics. It brings together a powerful set of partners covering fully the three key aspects - microwave engineering, chemistry and...

Recent human epidemiological and animal experimentation studies have revealed that negative conditions occurring prenatally influence the appearance of metabolic and cardiovascular diseases, some of which are in turn risk factors for Alzheimer’s disease (AD). The aim of this proposal is to determine if and how early-life stress may precipitate...

IMI’s growing neurodegenerative disorders (ND) portfolio is to get a new, dynamic platform – NEURONET – that will make it easier for the many projects to exploit synergies and connect the resources and needs of the different projects. NEURONET aims to be a key enabler and mediator across the portfolio, assisting in identifying gaps, multiplying...