The Oxford Control Brain Collection

The burden of brain diseases is increasing as our society ages. Few of these conditions are currently treatable. Although the last few years have seen a revolution in the genetics and subsequent modelling of diseases in the laboratory, this has not translated into significant progress for patients. It is increasingly recognised that breakthroughs in the field require the direct study of the human brain. In particular, it is important to understand how the expression of new risk genes for neurological disease is regulated in different regions of the normal brain in order to compare it with the disease state. Whilst prospective donation of brain tissue after death is encouraged from donors with specific diseases, this is not the case for donations from healthy individuals. This has resulted in a severe shortage of normal tissue which is essential as a comparator. It is known that when approached sensitively, next of kin are often willing to help with tissue donation following the death of a relative. Here we respond to a call by the MRC to help address the shortage of normal brain tissue donations after death. Oxford is well placed for this as we are experienced in brain banking and have a team of physicians and tissue liaison staff that work closely together. We are already involved in research that aims to improve the Coronial autopsy system and the donation of tissue for transplantation. We are also hosting the new Autism Brain Bank to support research into the biology of a common disease where hardly any tissue is currently available. People who participate in these studies will be asked to consider brain tissue donation for research. Here we ask for support to integrate the patient services for bereavement and transplant coordination to increase the donation of control brains. We anticipate that this approach will result in up to 50 new brain donations per year. With an additional laboratory assistant we will be in a position to ensure high quality tissue preservation and characterisation through our existing infrastructure and support by the Oxford Biomedical Research Centre. Any tissue collected through this approach will be made freely available for researchers via the new MRC UK Brain Banking network which operates at the highest ethical and scientific standards.

A MRC UK review of brain banking has identified a severe shortage of well characterised normal brains suitable for next generation molecular neuroscience research. A need to provide researchers with tissue from disorders that are common but rarely undergo autopsy such as autism has also been highlighted. Here we propose that the Thomas Willis Oxford Brain Collection (TWOBC) is well positioned to provide a solution to this problem. The TWOBC is part of the emerging MRC UK Brain Banking network, founding member of the Brains for Dementia (BDR) consortium, part of the MRC Cognitive Function and Aging Study (CFAS) and host of the newly formed Brain Bank for Autism. As part of the BDR study we recruit healthy elderly individuals which are cognitively assessed and have pledged their brains for research. However, these numbers are low. Here we propose to retrieve control brain and cord donations matched with blood and relevant peripheral tissues via our Coronial service and in collaboration with our heart valve tissue transplant team. The potential donor cohort in Oxford includes over 800 Coronial autopsies. We have piloted a combined post mortem CT/MRI study on 110 Coronial autopsies with minimal post-mortem delay, 90% of which would be suitable for brain donation based on normal brain CT. We have also identified over 150 potential brain donors per year via our heart valve tissue bank. We have recently received support from the NIHR Oxford Biomedical Research Centre to establish routine DNA/mRNA/protein extraction and quality control protocols in neuropathology. We are actively collaborating with local basic scientists to establish sampling protocols for the application of next generation sequencing techniques to brain tissue. Infrastructure consists of newly built state-of-the art laboratories and tissue storage facilities with space for expansion. This is a single-site application based around a team of neuropathologists, general pathologists, and the directors of the Oxford heart valve bank and patient services (including bereavement). With the requested support we will fuse the heart valve and bereavement team services. Based on the above numbers we estimate that we will be able to collect 30 to 50 well-characterised control brains per annum and make them available for researchers. Some of these brains will have the added value of corresponding high-resolution post-mortem CT or MRI data which we would make freely available for researchers. We are fully HTA and CPA accredited and governance structures, consent and ethics protocols are established.