Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Brain banking: opportunities, challenges and meaning for the future

Nature Reviews Neuroscience volume 10, pages 70–78 (2009)Cite this article

Abstract

Brain banks collect post-mortem human brains to foster research into human CNS function and disease. They have been indispensable for uncovering the secrets of many diseases, including Alzheimer's and Parkinson's. At a time when there are so many open questions in neuroscience and the incidence of brain diseases continues to increase in parallel with the aging of the population, brain banking remains at the heart of brain research. However, the major source of brain banks, the clinical autopsy, is rapidly falling into limbo. New strategies, including donor programmes, medico-legal autopsies and banking in networks, as well as fresh considerations of the ethics and public relations, are required.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A world map of brain banks.
Figure 2: Brain banking and longitudinal studies of disease progression.
Figure 3: The worldwide declining autopsy rate.

Similar content being viewed by others

References

  1. Alzheimer, A., Stelzmann, R. A., Schnitzlein, H. N. & Murtagh, F. R. An English translation of Alzheimer's 1907 paper, “Über eine eigenartige Erkankung der Hirnrinde”. Clin. Anat. 8, 429–431 (1995).

    CAS  PubMed  Google Scholar 

  2. Glenner, G. G. & Wong, C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120, 885–890 (1984).

    CAS  PubMed  Google Scholar 

  3. Masters, C. L. et al. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Natl Acad. Sci. USA 82, 4245–4249 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kosik, K. S., Joachim, C. L. & Selkoe, D. J. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc. Natl Acad. Sci. USA 83, 4044–4048 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Mann, D. M. et al. Preferential deposition of amyloid beta protein (Aβ) in the form Aβ40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele. Neurosci. Lett. 221, 81–84 (1997).

    CAS  PubMed  Google Scholar 

  6. McCarron, M. O. et al. The apolipoprotein E ε2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J. Neuropathol. Exp. Neurol. 58, 711–718 (1999).

    CAS  PubMed  Google Scholar 

  7. Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239–259 (1991).

    CAS  PubMed  Google Scholar 

  8. Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H. & Del Tredici, K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 112, 389–404 (2006).

    PubMed  PubMed Central  Google Scholar 

  9. Thal, D. R., Rub, U., Orantes, M. & Braak, H. Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58, 1791–1800 (2002).

    PubMed  Google Scholar 

  10. Olesen, J. & Leonardi, M. The burden of brain diseases in Europe. Eur. J. Neurol. 10, 471–477 (2003).

    CAS  PubMed  Google Scholar 

  11. Cruz-Sanchez, F. F. & Tolosa, E. The need of a consensus for brain banking. J. Neural Transm. Suppl. 39, 1–4 (1993).

    CAS  PubMed  Google Scholar 

  12. Davies, J., Everall, I. P. & Lantos, P. L. The contemporary AIDS database and brain bank—lessons from the past. J. Neural Transm. Suppl. 39, 77–85 (1993).

    CAS  PubMed  Google Scholar 

  13. Tourtelotte, W. Avant propos: a human specimen bank and brain biopsies. Riv. Patol. Nerv. Ment. 91, 255–262 (1970).

    Google Scholar 

  14. Spillantini, M. G. et al. α-synuclein in Lewy bodies. Nature 388, 839–840 (1997).

    CAS  PubMed  Google Scholar 

  15. Kahle, P. J. et al. Subcellular localization of wild-type and Parkinson's disease-associated mutant α-synuclein in human and transgenic mouse brain. J. Neurosci. 20, 6365–6373 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Neumann, M. et al. Misfolded proteinase K-resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies. J. Clin. Invest. 110, 1429–1439 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990–1993 (1997).

    CAS  PubMed  Google Scholar 

  18. Radde, R., Duma, C., Goedert, M. & Jucker, M. The value of incomplete mouse models of Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging 35 (Suppl. 1), S70–S74 (2008).

    CAS  PubMed  Google Scholar 

  19. Braak, H. et al. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging 24, 197–211 (2003).

    PubMed  Google Scholar 

  20. Vonsattel, J. P. et al. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 44, 559–577 (1985).

    CAS  PubMed  Google Scholar 

  21. Fernando, M. S. & Ince, P. G. Vascular pathologies and cognition in a population-based cohort of elderly people. J. Neurol. Sci. 226, 13–17 (2004).

    PubMed  Google Scholar 

  22. Duyckaerts, C., Potier, M. C. & Delatour, B. Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol. 115, 5–38 (2008).

    PubMed  Google Scholar 

  23. Harding, A. J., Wong, A., Svoboda, M., Kril, J. J. & Halliday, G. M. Chronic alcohol consumption does not cause hippocampal neuron loss in humans. Hippocampus 7, 78–87 (1997).

    CAS  PubMed  Google Scholar 

  24. Kutzelnigg, A. et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128, 2705–2712 (2005).

    PubMed  Google Scholar 

  25. Roemer, S. F. et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 130, 1194–1205 (2007).

    PubMed  Google Scholar 

  26. Trapp, B. D. et al. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 338, 278–285 (1998).

    CAS  PubMed  Google Scholar 

  27. Serafini, B. et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J. Exp. Med. 204, 2899–2912 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Frank, S., Clavaguera, F. & Tolnay, M. Tauopathy models and human neuropathology: similarities and differences. Acta Neuropathol. 115, 39–53 (2008).

    PubMed  Google Scholar 

  29. Neumann, M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133 (2006).

    CAS  PubMed  Google Scholar 

  30. Sreedharan, J. et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668–1672 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Enard, W. et al. Intra- and interspecific variation in primate gene expression patterns. Science 296, 340–343 (2002).

    CAS  PubMed  Google Scholar 

  32. Myers, A. J. et al. A survey of genetic human cortical gene expression. Nature Genet. 39, 1494–1499 (2007).

    CAS  PubMed  Google Scholar 

  33. Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007).

    CAS  PubMed  Google Scholar 

  34. Markram, H. Bioinformatics: industrializing neuroscience. Nature 445, 160–161 (2007).

    CAS  PubMed  Google Scholar 

  35. Simic, G. et al. Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area. Neuroscience 89, 73–89 (1999).

    CAS  PubMed  Google Scholar 

  36. Preuss, T. M. Taking the measure of diversity: comparative alternatives to the model-animal paradigm in cortical neuroscience. Brain Behav. Evol. 55, 287–299 (2000).

    CAS  PubMed  Google Scholar 

  37. Akbarian, S. et al. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J. Neurosci. 16, 19–30 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Byne, W. et al. Schizophrenia and sex associated differences in the expression of neuronal and oligodendrocyte-specific genes in individual thalamic nuclei. Schizophr. Res. 98, 118–128 (2008).

    PubMed  Google Scholar 

  39. Iwamoto, K., Bundo, M. & Kato, T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum. Mol. Genet. 14, 241–253 (2005).

    CAS  PubMed  Google Scholar 

  40. Harrison, P. J. & Owen, M. J. Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet 361, 417–419 (2003).

    CAS  PubMed  Google Scholar 

  41. Nakamura, N. et al. Laser capture microdissection for analysis of single cells. Methods Mol. Med. 132, 11–18 (2007).

    CAS  PubMed  Google Scholar 

  42. Ferrer, I. et al. Effects of formalin fixation, paraffin embedding, and time of storage on DNA preservation in brain tissue: a BrainNet Europe study. Brain Pathol. 17, 297–303 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Ferrer, I. et al. Brain protein preservation largely depends on the postmortem storage temperature: implications for study of proteins in human neurologic diseases and management of brain banks: a BrainNet Europe Study. J. Neuropathol. Exp. Neurol. 66, 35–46 (2007).

    CAS  PubMed  Google Scholar 

  44. Ronaghi, M., Karamohamed, S., Pettersson, B., Uhlen, M. & Nyren, P. Real-time DNA sequencing using detection of pyrophosphate release. Anal. Biochem. 242, 84–89 (1996).

    CAS  PubMed  Google Scholar 

  45. Harrison, P. J. et al. The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins. Neurosci. Lett. 200, 151–154 (1995).

    CAS  PubMed  Google Scholar 

  46. Chevyreva, I., Faull, R. L., Green, C. R. & Nicholson, L. F. Assessing RNA quality in postmortem human brain tissue. Exp. Mol. Pathol. 84, 71–77 (2008).

    CAS  PubMed  Google Scholar 

  47. Stan, A. D. et al. Human postmortem tissue: what quality markers matter? Brain Res. 1123, 1–11 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Xiang, W. et al. Cerebral gene expression profiles in sporadic Creutzfeldt-Jakob disease. Ann. Neurol. 58, 242–257 (2005).

    CAS  PubMed  Google Scholar 

  49. McShea, A. et al. The application of microarray technology to neuropathology: cutting edge tool with clinical diagnostics potential or too much information? J. Neuropathol. Exp. Neurol. 65, 1031–1039 (2006).

    CAS  PubMed  Google Scholar 

  50. Marcotte, E. R., Srivastava, L. K. & Quirion, R. cDNA microarray and proteomic approaches in the study of brain diseases: focus on schizophrenia and Alzheimer's disease. Pharmacol. Ther. 100, 63–74 (2003).

    CAS  PubMed  Google Scholar 

  51. Miller, J. A., Oldham, M. C. & Geschwind, D. H. A systems level analysis of transcriptional changes in Alzheimer's disease and normal aging. J. Neurosci. 28, 1410–1420 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Witchell, J., Varshney, D., Gajjar, T., Wangoo, A. & Goyal, M. RNA isolation and quantitative PCR from HOPE- and formalin-fixed bovine lymph node tissues. Pathol. Res. Pract. 204, 105–111 (2008).

    CAS  PubMed  Google Scholar 

  53. Wang, W. X. et al. The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of β-site amyloid precursor protein-cleaving enzyme 1. J. Neurosci. 28, 1213–1223 (2008).

    PubMed  PubMed Central  Google Scholar 

  54. Kim, J. et al. A microRNA feedback circuit in midbrain dopamine neurons. Science 317, 1220–1224 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Burmistrova, O. A. et al. MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11). Biochemistry (Mosc.) 72, 578–582 (2007).

    CAS  Google Scholar 

  56. Hansen, T. et al. Brain expressed microRNAs implicated in schizophrenia etiology. PLoS ONE 2, e873 (2007).

    PubMed  PubMed Central  Google Scholar 

  57. Lukiw, W. J. Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus. Neuroreport 18, 297–300 (2007).

    CAS  PubMed  Google Scholar 

  58. Siew, L. K., Love, S., Dawbarn, D., Wilcock, G. K. & Allen, S. J. Measurement of pre- and post-synaptic proteins in cerebral cortex: effects of post-mortem delay. J. Neurosci. Methods 139, 153–159 (2004).

    CAS  PubMed  Google Scholar 

  59. Ferrer, I., Martinez, A., Boluda, S., Parchi, P. & Barrachina, M. Brain banks: benefits, limitations and cautions concerning the use of post-mortem brain tissue for molecular studies. Cell Tissue Bank. 9, 181–194 (2008).

    CAS  PubMed  Google Scholar 

  60. Dalfo, E., Barrachina, M., Rosa, J. L., Ambrosio, S. & Ferrer, I. Abnormal α-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease. Neurobiol. Dis. 16, 92–97 (2004).

    CAS  PubMed  Google Scholar 

  61. Boutillier, S. et al. Sp3 and sp4 transcription factor levels are increased in brains of patients with Alzheimer's disease. Neurodegener. Dis. 4, 413–423 (2007).

    CAS  PubMed  Google Scholar 

  62. Yao, J. K., Leonard, S. & Reddy, R. D. Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr. Res. 42, 7–17 (2000).

    CAS  PubMed  Google Scholar 

  63. Schmitt, A. et al. Altered thalamic membrane phospholipids in schizophrenia: a postmortem study. Biol. Psychiatry 56, 41–45 (2004).

    CAS  PubMed  Google Scholar 

  64. Nicoll, J. A. et al. Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report. Nature Med. 9, 448–452 (2003).

    CAS  PubMed  Google Scholar 

  65. Ferrer, I., Boada Rovira, M., Sanchez Guerra, M. L., Rey, M. J. & Costa-Jussa, F. Neuropathology and pathogenesis of encephalitis following amyloid-β immunization in Alzheimer's disease. Brain Pathol. 14, 11–20 (2004).

    CAS  PubMed  Google Scholar 

  66. Burton, J. L. & Underwood, J. C. Necropsy practice after the “organ retention scandal”: requests, performance, and tissue retention. J. Clin. Pathol. 56, 537–541 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Millar, T. et al. Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank. J. Pathol. 213, 369–375 (2007).

    CAS  PubMed  Google Scholar 

  68. Bell, J. E. et al. Management of a twenty-first century brain bank: experience in the BrainNet Europe consortium. Acta Neuropathol. 115, 497–507 (2008).

    PubMed  Google Scholar 

  69. Hughes, A. J., Ben-Shlomo, Y., Daniel, S. E. & Lees, A. J. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. 1992. Neurology 57, S34–S38 (2001).

    CAS  PubMed  Google Scholar 

  70. Barker, W. W. et al. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis. Assoc. Disord. 16, 203–212 (2002).

    PubMed  Google Scholar 

  71. Alafuzoff, I. et al. Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe consortium. Brain Pathol. 18, 484–496 (2008).

    PubMed  PubMed Central  Google Scholar 

  72. Alafuzoff, I. et al. Assessment of α-synuclein pathology: a study of the BrainNet Europe consortium. J. Neuropathol. Exp. Neurol. 67, 125–143 (2008).

    PubMed  Google Scholar 

  73. Alafuzoff, I. et al. Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe consortium. J. Neuropathol. Exp. Neurol. 65, 740–757 (2006).

    CAS  PubMed  Google Scholar 

  74. Alafuzoff, I. et al. Inter-laboratory comparison of neuropathological assessments of β-amyloid protein: a study of the BrainNet Europe consortium. Acta Neuropathol. 115, 533–546 (2008).

    CAS  PubMed  Google Scholar 

  75. Seilhean, D. [Autopsy and religions]. Bull. Acad. Natl. Med. 185, 877–887; discussion 888–889 (2001).

    CAS  PubMed  Google Scholar 

  76. Boyes, M. & Ward, P. Brain donation for schizophrenia research: gift, consent, and meaning. J. Med. Ethics 29, 165–168 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Hulette, C. M. Brain banking in the United States. J. Neuropathol. Exp. Neurol. 62, 715–722 (2003).

    PubMed  Google Scholar 

  78. Schmitt, A. et al. How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II. J. Neural Transm. 114, 527–537 (2007).

    CAS  PubMed  Google Scholar 

  79. Vonsattel, J. P., Del Amaya, M. P. & Keller, C. E. Twenty-first century brain banking. Processing brains for research: the Columbia University methods. Acta Neuropathol. 115, 509–532 (2008).

    PubMed  Google Scholar 

  80. Murphy, D. D. & Ravina, B. Brain banking for neurodegenerative diseases. Curr. Opin. Neurol. 16, 459–463 (2003).

    PubMed  Google Scholar 

  81. Braak, H., Rüb, U., Schultz, C. & Del Tredici, K. in Alzheimer's Disease: A Century of Scientific and Clinical Research (eds Perry, G., Avila, J., Kinoshita, J. & Smith, M. A.) 35–44 (IOS Press, 2006).

    Google Scholar 

  82. WHO Regional Office for Europe. Health for All database (HFA-DB). World Health Organization Regional Office for Europe [online], (2008).

  83. Burton, J. L. & Underwood, J. Clinical, educational, and epidemiological value of autopsy. Lancet 369, 1471–1480 (2007).

    PubMed  Google Scholar 

Download references

Acknowledgements

The existence of brain banks is dependent on the generosity of individuals and their relatives who are willing to donate tissues for research purposes. BrainNet Europe is supported by the European Community's Sixth Framework Programme (LSMH-CT-2004-503,039); BrainNet, a collaboration of German Brain banks, is funded by the Federal Ministry of Education and Research. This paper reflects only the author's views and the Community is not liable for any use that may be made of the information contained herein.

Author information

Authors and Affiliations

  1. Hans Kretzschmar is at the Institute of Neuropathology, Feodor-Lynen-Strasse 23, Munich, 81377, Germany; at BrainNet; and at BrainNet Europe. hans.kretzschmar@med.uni-muenchen.de,

    Hans Kretzschmar

  2. at BrainNet,

    Hans Kretzschmar

Authors
  1. Hans Kretzschmar
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Supplementary Information S1 (box)

Brain banks worldwide (PDF 301 kb)

A list of national and international brain bank networks and brain banks.

Related links

Related links

DATABASES

OMIM

AD

ALS

frontotemporal lobar degeneration

Huntington's disease

PD

Pick's disease

progressive supranuclear palsy

FURTHER INFORMATION

Hans Kretzschmar's homepage

BrainNet

BrainNet europe

Allen institute for Brain science

the Bundesärztekammer

statistik Austria

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kretzschmar, H. Brain banking: opportunities, challenges and meaning for the future. Nat Rev Neurosci 10, 70–78 (2009). https://doi.org/10.1038/nrn2535

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2535

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing