Research Projects

DECIDE (Diagnostic Enhancement of Confidence by an International Distributed Environment), aims at creating a e-Infrastructure to enhance the diagnostic confidence in chronic brain diseases such as Alzheimer and dementia. Proper management of these neurodegenerative diseases are thought to be very important in terms of health-economical point of...

Neurodegenerative diseases are triggered by protein aggregation in the CNS, but developing therapies has been challenging. Since key disease mechanisms change during disease progression, halting further neuron loss has not been achieved and may not even improve the symptoms and survival. Causal therapy is most realistic for monogenic disease...

Alzheimer's disease (AD) is the most common neurodegenerative disorder and is incurable. A drug candidate specifically inhibiting butyrylcholinesterase (BChE) activity will lead to improved clinical outcome in the treatment of AD. The fellow Qiong Shen (QS) has extensive experience, knowledge and technical skills in research into AD. Previously she...

Alzheimer’s disease is a neurodegenerative disease characterized by the accumulation of proteins and protein fragments in the brain, progressive neuronal loss, inflammation, and the gradual and inevitable decline of memory and cognition. Decline of memory and cognition is coupled with binding of β amyloid peptides (Aβ) and their derived diffusible...

Normal aging is associated with declines in episodic memory and executive functions. Research suggests that around 20-50% of clinically healthy individuals show significant accumulation of amyloid, one of the hallmark biomarkers of Alzheimer’s disease but it has been difficult to establish the functional impact of amyloid burden in healthy older...

Neurodegenerative disorders represent the most important medical, social and financial challenges for the 21st century. In 2018, the world counts 50 million people with Alzheimer’s disease and 7 million with Parkinson’s disease, and the number of cases will double before 2050. The current medical paradigms, which incriminate amyloid plaques as the...

Worlwide, about 60 million people have some kind of difficulty in walking, which is related to some neurological disorder (stroke, dementia, neuromuscular diseases, etc). Roughly 40 million of affected correspond to elders and the % is higher in Europe. The remaining is the sum of physically disabled by cerebral palsy (14 million), neuromuscular...

Fibrillar deposits of proteins are the hallmark of amyloid diseases, amongst which Alzheimer’s disease stands out as the most widespread neurodegenerative pathology of the brain. Neuronal dysfunction is currently attributed to the interaction of A-beta oligomers with the plasma membrane. Several scenarios have been proposed, but the mechanisms of...

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...

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...