Editorial
Research using human brain tissue has had a pivotal role in advancing our understanding of the biological basis of diseases of the nervous system. With increasing numbers of people likely to be affected by such disorders in the future, research on human brain samples continues to be of paramount importance. As highlighted by a Review in The Lancet Neurology, to meet the need for high-quality samples, brain banks have been set up in many countries, and networks of brain banks established to optimise supply of well characterised brain tissue. However, a more effective approach to soliciting donations and tissue collection is needed if insights into the evolution of the pathology of brain diseases are to be forthcoming. Spontaneous altruistic individual brain donations have been the main source of brain bank material to date and, although these will continue to be valuable, there is often limited ante-mortem clinical information available for these samples. Furthermore, tissue from spontaneous donations is predominantly from end-stage disease and information on the disease at earlier stages is scarce. A more valuable approach is to solicit donations from participants in longitudinal cohort studies; the advantages of such cohorts are the availability of extensive clinical information (including MRI data, genetic data, biomarkers, and cognitive function), details on lifestyle and comorbidities, and the potential to obtain samples from patients who might die at an earlier stage of disease. For the principal investigators of these studies, post-mortem neuropathological diagnosis, undertaken by brain banks, is important to confirm the clinical diagnosis. Furthermore, these cohorts often include individuals who are free from overt neurological disease; such controls are crucial for comparison and are thus just as important as patients. Identification of cohorts to approach for brain donation should be science-driven, based on need and then targeting cohorts that are most informative. Spontaneous donations should still be encouraged, but a balance needs to be struck between these two approaches. To increase the pool of brains available, brain donation could also be considered as an option for people who join national organ donor registers. Public consultations have consistently shown that the public is supportive of brain donation; however, brain donation for research via organ donation registers is not an option in most www.thelancet.com/neurology Vol 12 November 2013
countries. And in countries that do include the option to donate tissue for research, such as Sweden, legal hindrances often prevent tissue from being taken. Many disorders of the nervous system are systemic diseases, and there is increasing interest from researchers in obtaining non-CNS tissue samples in addition to the brain. Although whole-body donation is likely to be logistically challenging, targeted biopsy of other organs would be more feasible. For example, translational studies are in progress to establish whether Parkinson’s disease can be diagnosed with peripheral tissue biopsy. Thus, samples of appendix, colon, and intestine might lead to new insights. And the immune system has a role, not only in disorders such as multiple sclerosis, but in Alzheimer’s disease and other neurodegenerative diseases, so availability of blood or immune cells, or immune organs could be important. New methods, such as transcriptomics, proteomics, and lipidomics, are available to study the molecular pathology of neurodegenerative conditions, but tissue needs to be retrieved and processed quickly (ideally within 12 h) to minimise degradation. In some countries, such as the Netherlands and some regions of the USA, because of geographic proximity to brain banks, streamlined regulatory processes, and good communication, brains donated for research can be retrieved very rapidly, often within a few hours of death. However, in countries such as the UK, regulatory hurdles related to death certification prolong the interval between death and brain retrieval, and delays can have an adverse effect on the quality of the tissue. The scientific and clinical communities need to work with regulatory bodies and health services to streamline processes to avoid unnecessary delays. The importance of brain banking to our understanding of neurological diseases cannot be understated. Even if these strategies to improve donation are successful, the time between individuals agreeing to become brain donors and their donation can be lengthy, so the situation is unlikely to change soon. Thus, the samples collected need to be of most value to scientists and optimally used. Regular dialogue between brain banks, researchers, and patient groups will help to identify priorities and how to achieve them, to allow further inroads to be made into diseases of the nervous system. ■ The Lancet Neurology
James King-Homles/Science Photo Library
Brain banking: more effective strategies needed
See Review page 1096
1035
Research using human brain tissue has had a pivotal role in advancing our understanding of the biological basis of diseases of the nervous system. With increasing numbers of people likely to be affected by such disorders in the future, research on human brain samples continues to be of paramount importance. As highlighted by a Review in The Lancet Neurology, to meet the need for high-quality samples, brain banks have been set up in many countries, and networks of brain banks established to optimise supply of well characterised brain tissue. However, a more effective approach to soliciting donations and tissue collection is needed if insights into the evolution of the pathology of brain diseases are to be forthcoming. Spontaneous altruistic individual brain donations have been the main source of brain bank material to date and, although these will continue to be valuable, there is often limited ante-mortem clinical information available for these samples. Furthermore, tissue from spontaneous donations is predominantly from end-stage disease and information on the disease at earlier stages is scarce. A more valuable approach is to solicit donations from participants in longitudinal cohort studies; the advantages of such cohorts are the availability of extensive clinical information (including MRI data, genetic data, biomarkers, and cognitive function), details on lifestyle and comorbidities, and the potential to obtain samples from patients who might die at an earlier stage of disease. For the principal investigators of these studies, post-mortem neuropathological diagnosis, undertaken by brain banks, is important to confirm the clinical diagnosis. Furthermore, these cohorts often include individuals who are free from overt neurological disease; such controls are crucial for comparison and are thus just as important as patients. Identification of cohorts to approach for brain donation should be science-driven, based on need and then targeting cohorts that are most informative. Spontaneous donations should still be encouraged, but a balance needs to be struck between these two approaches. To increase the pool of brains available, brain donation could also be considered as an option for people who join national organ donor registers. Public consultations have consistently shown that the public is supportive of brain donation; however, brain donation for research via organ donation registers is not an option in most www.thelancet.com/neurology Vol 12 November 2013
countries. And in countries that do include the option to donate tissue for research, such as Sweden, legal hindrances often prevent tissue from being taken. Many disorders of the nervous system are systemic diseases, and there is increasing interest from researchers in obtaining non-CNS tissue samples in addition to the brain. Although whole-body donation is likely to be logistically challenging, targeted biopsy of other organs would be more feasible. For example, translational studies are in progress to establish whether Parkinson’s disease can be diagnosed with peripheral tissue biopsy. Thus, samples of appendix, colon, and intestine might lead to new insights. And the immune system has a role, not only in disorders such as multiple sclerosis, but in Alzheimer’s disease and other neurodegenerative diseases, so availability of blood or immune cells, or immune organs could be important. New methods, such as transcriptomics, proteomics, and lipidomics, are available to study the molecular pathology of neurodegenerative conditions, but tissue needs to be retrieved and processed quickly (ideally within 12 h) to minimise degradation. In some countries, such as the Netherlands and some regions of the USA, because of geographic proximity to brain banks, streamlined regulatory processes, and good communication, brains donated for research can be retrieved very rapidly, often within a few hours of death. However, in countries such as the UK, regulatory hurdles related to death certification prolong the interval between death and brain retrieval, and delays can have an adverse effect on the quality of the tissue. The scientific and clinical communities need to work with regulatory bodies and health services to streamline processes to avoid unnecessary delays. The importance of brain banking to our understanding of neurological diseases cannot be understated. Even if these strategies to improve donation are successful, the time between individuals agreeing to become brain donors and their donation can be lengthy, so the situation is unlikely to change soon. Thus, the samples collected need to be of most value to scientists and optimally used. Regular dialogue between brain banks, researchers, and patient groups will help to identify priorities and how to achieve them, to allow further inroads to be made into diseases of the nervous system. ■ The Lancet Neurology
James King-Homles/Science Photo Library
Brain banking: more effective strategies needed
See Review page 1096
1035
