Program leaders:            Wiesje van der Flier, Rob de Bie
Taskforce team:              Henk Berendse, Charlotte Teunissen and Paul Lucassen
Program members


Rationale and common goals

Neurodegenerative disorders, particularly Alzheimer’s disease (AD), other forms of dementia and Parkinson’s disease (PD), are among the biggest health care challenges of the 21st century. There are now over 250,000 dementia patients and 40,000 patients of Parkinson’s disease in the Netherlands. Because no treatments can stop these neurodegenerative disorders amid the backdrop of an aging population, numbers are expected to rise further quickly. This poses a direct threat to the sustainability of our entire health care system. The development of treatments that stop, prevent or at least slow down the degenerative processes is crucial to reduce future costs associated with neurodegenerative disorders and hence keep our health care system viable.

Neurodegenerative disorders share a profound pathophysiological and clinical complexity. For the majority of patients, multiple causes in concert lead to the development of disease, which unfolds over the course of years, probably decades. A careful clinical evaluation is the corner stone for a valid diagnosis of any neurodegenerative disorder. Moreover, it provides fundamental insight into the basic mechanisms that are critical for the development and validation of animal models and biomarkers. To date, treatment is limited to alleviation of symptoms, but our ultimate goal is to recognize disease before it manifests clinically, understand disease mechanisms and subsequently modify the disease process to prevent progression to a full blown disease state. This goal can only be achieved by improving early diagnostics, understanding clinical heterogeneity and mixed pathologies, and unraveling underlying mechanisms in patients and relevant model systems. We are in an excellent position to execute an integrative research program tailored to these aims. New technologies and in-house assets are the necessary prerequisites for success.

Assets

Our major assets are large and unique patient cohorts (Amsterdam Dementia Cohort: ~n=5000; Parkinson cohort: ~n=1000), large biobanks, extensive (multi-modal) brain imaging facilities and clinical trials. We have a strong tradition in translational research with excellent facilities. There is a longstanding and close collaboration with the Dutch brain bank and a history of research on post mortem tissue. Furthermore, we have ample experience in executing both complex, high-end clinical trials and large nationwide clinical trials. There is extensive expertise in clinical research, generation of well-characterized patient cohorts, clinical (endo)phenotyping (including advanced imaging using MRI, PET, EEG/MEG), as well as studies of (novel) biomarkers, neuroanatomy, neuropathology, transcriptomics, proteomics, gene finding, functional characterization, cellular and animal models. A major challenge of the program is to further emphasize synergistic approaches that can lead to breakthrough findings.

Translational links: clinical observation by passionate clinicians

The starting point and inspiration are careful clinical observation of our patients by passionate clinicians. Clinical data collected in the patient setting form the basis for our clinical research activities, and they also form the inspiration for basic science aiming to unravel the underlying brain disease mechanisms (i.e. bedside to bench). In turn, state of the art basic science aims to provide and test targets for the better diagnostic and prognostic biomarkers, and the development of novel or improved treatment (bench to bedside). Use of patient biomaterial and developing new approaches in employing patient-derived cells will boost this effort. We are fully equipped to test novel treatments (infrastructure and CRO services for Phase I-III studies are available).

Making the difference?

  • This program is truly translational, capitalizing on observational studies, basic science and intervention studies, with the ultimate aim to reduce the number of patients with neurodegenerative disorders, and to reduce the burden of neurodegenerative brain diseases for society at large;
  • We aim to achieve world-class research in:
    o   Early diagnostics;
    o   Subtypes/endophenotypes; and
    o   Treatments optimizing current treatments and developing novel treatments to cure or prevent neurodegeneration, including mechanistic studies to provide input for this latter goal;
  • Crossing boundaries of individual diseases to unravel specific versus generic neurodegenerative processes.