The NBB
The NBB is a research infrastructure that collects human brain tissue of donors with a variety of neurological and psychiatric disorders and control donors. Since 1985, NBB collected brain samples from 5,000 donors. The samples, together with an anonymized summary of a donor’s medical record and neuropathological assessment, are sent to nearly 300 academic institutes and 75 companies worldwide. The ultimate aim is increasing our understanding of the human brain and to support research focused on improving diagnosis and treatment of brain diseases.
NBB collects samples rapidly after dead. Due to a short postmortem delay of 6.5 h on average, brain samples are highly suitable for state-of-the-art molecular research techniques. NBB provides frozen and fixed brain samples and matched biofluids including postmortem CSF.
Priorities
As part of the Netherlands Neurogenetics Database (NND) collaboration with University Medical Center Groningen, clinical and neuropathological signs and symptoms are extracted from the original data using machine learning algorithms. Together with genetic single polynucleotide data, information will be combined to compute Polygenic Risk Scores (PRS) for several brain diseases.
The NBB has initiated specific donor programs for multiple sclerosis (NBB-MS) and psychiatric diseases (NBB-Psy). The pathology of MS is complex and demands specific analyses such as post-mortem MRI localization of pathology and characterization of all tissue blocks for tissue dissemination. NBB-Psy increases the availability of brain tissue of subjects suffering from psychiatric diseases, which is scare worldwide. Currently, nearly 1,500 donors with a psychiatric disease are registered at NBB.
Research facilitated by NBB
NBB tissue contributes to international fundamental and applied preclinical or translational research.
Research questions that can be addressed through the services of the Netherlands Brain Bank:
1. What are the cellular and molecular pathways causing neurological and psychiatric symptoms?
Next to immunohistochemical approaches, multiplex imaging and ultrastructural analyses of human brain tissue have become possible. Also high resolution multi-omics techniques are now available, e.g. single cell and spatial RNA sequencing, ATAC seq, (single cell) proteomics, lipidomics and metabolomics. For these techniques well characterized human brain tissue of high quality with short post mortem delay are needed to identify targets for therapy.
2. Can variability of neurological and psychiatric symptoms be linked to neuropathological variability?
The only site where clinical and neuropathological data come together structurally, is at a brain bank facility. Up to 30% of the neurological diagnoses are not confirmed neuropathologically. There are no routine brain autopsies and neuropathological diagnoses performed at the UMC’s, due to lack of reimbursement. At NBB, clinical data and neuropathological features can be compared and subtypes of disease identified. The Netherlands Neurogenetics Database was set up by the NBB to allows such analyses.
3. How does genetic vulnerability to brain diseases translate to molecular changes in the brain causing or impacting on disease progression?
DNA sequencing of all NBB brain donors allows identification of known and unknown variants and study of molecular changes in the brain tissue relating to genetic background.