Overview
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institutions_harvard_brain_tis["Harvard Brain Tissue Resource Center"]
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institutions_harvard_0["Mission"]
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institutions_harvard_1["Collection Focus"]
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institutions_harvard_2["Neurodegenerative Disease Collection"]
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institutions_harvard_3["Research Contributions"]
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institutions_harvard_4["Notable Discoveries"]
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institutions_harvard_5["Collection Protocols"]
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...Overview
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The Harvard Brain Tissue Resource Center (HBTRC), formerly known as the Harvard Brain Bank, is one of the United States' premier brain tissue repositories for neurodegenerative and psychiatric research. Located at McLean Hospital in Belmont, Massachusetts, the HBTRC is funded by the National Institute of Mental Health (NIMH) and provides postmortem brain tissue to qualified researchers worldwide.
Founded in 1986, the HBTRC has served as a critical resource for the neuroscience community, supporting over 3,000 research projects and distributing more than 50,000 tissue samples to investigators globally. The center maintains rigorous quality control standards and comprehensive documentation for all specimens, making it an invaluable resource for understanding the neurobiological basis of brain disorders.
Mission
The HBTRC's mission is to advance the understanding of psychiatric and neurological disorders by:
- Collecting and preserving high-quality postmortem brain tissue
- Supporting research on the neurobiological basis of brain disorders
- Maintaining detailed clinical and demographic information
- Facilitating collaboration between basic and clinical researchers
- Providing educational resources on brain banking and neuropathology
Collection Focus
The HBTRC maintains one of the largest brain tissue collections in the world:
| Category | Focus Areas |
|----------|-------------|
| Neuropsychiatric | Schizophrenia, bipolar disorder, depression |
| Neurodegenerative | Alzheimer's disease, Parkinson's disease, ALS |
| Developmental | Autism, intellectual disabilities |
| Normal | Age-matched controls |
Neurodegenerative Disease Collection
The center's neurodegenerative disease collection includes:
- Alzheimer's Disease: Over 400 cases with confirmed clinical and neuropathological diagnosis
- Parkinson's Disease: More than 200 cases with Lewy body pathology
- Amyotrophic Lateral Sclerosis (ALS): Approximately 150 cases with TDP-43 pathology
- Frontotemporal Dementia: Cases with tau, TDP-43, and FUS pathology
- Lewy Body Dementia: Cases with cortical and brainstem Lewy bodies
- Vascular Dementia: Cases with significant cerebrovascular pathology
Each case includes detailed clinical information, including:
- Comprehensive neuropsychological testing results
- Medical history and medication records
- Family history of neurological disease
- Braak staging for neurofibrillary tangles
- Thal phase for amyloid deposition
- CERAD plaque scores
Research Contributions
The HBTRC has supported thousands of research projects:
Neuroimaging studies: Validating PET ligands for amyloid and tau imaging
Genetic studies: GWAS and whole-exome sequencing projects identifying disease risk variants
Protein analysis: Biomarker discovery and validation studies
Cellular studies: Neuropathology investigations of disease mechanisms
Gene expression studies: Transcriptomic and epigenomic analyses
Stem cell research: Induced pluripotent stem cell derivation for disease modelingNotable Discoveries
Research using HBTRC tissue has contributed to numerous landmark discoveries:
- Validation of amyloid PET ligands (Florbetapir, Florbetaben, Flortaucipir)
- Identification of novel Alzheimer's disease risk genes (PLD3, TREM2)
- Characterization of tau propagation mechanisms
- Discovery of TDP-43 pathology in ALS and frontotemporal dementia
- Understanding of alpha-synuclein Lewy body formation
Collection Protocols
The HBTRC employs standardized collection protocols to ensure tissue quality:
Brain Retrieval
- Rapid postmortem interval (average <12 hours)
- Systematic hemisphere dissection
- Flash-freezing of tissue blocks in liquid nitrogen
- Paraffin embedding for histological studies
Quality Assurance
- Regular monitoring of RNA integrity numbers (RIN)
- Neuropathological confirmation by board-certified neuropathologists
- Standardized fixation protocols for immunostaining
- Inventory tracking with complete case documentation
Access Procedures
Researchers can access HBTRC tissue through:
Application submission describing research objectives
Scientific review by external committee
Institutional IRB approval
Material transfer agreement
Tissue distribution and shippingApplication Requirements
- Detailed research proposal
- Funding confirmation
- Laboratory capabilities for tissue processing
- IRB approval documentation
- CV and publication record
Collaborations and Partnerships
The HBTRC maintains active collaborations with:
- NIH Neurobiology of Disease Brain Banks Consortium
- Alzheimer's Disease Neuroimaging Initiative (ADNI)
- Parkinson's Progression Markers Initiative (PPMI)
- National Center for Advancing Translational Sciences (NCATS)
- International Brain Bank Coordinating Committee
Training Programs
The center offers training opportunities for researchers:
- Brain bank operation and management
- Neuropathological assessment techniques
- Tissue preparation for various applications
- Quality control and data management
Statistics and Impact
The HBTRC by the numbers:
- Over 3,000 brains in collection
- More than 50,000 tissue samples distributed
- 500+ active research projects annually
- 200+ collaborating institutions worldwide
- 1,000+ peer-reviewed publications utilizing HBTRC tissue
Governance and Funding
The HBTRC is supported by:
- National Institute of Mental Health (NIMH)
- National Institute on Aging (NIA)
- Private foundation grants
- Corporate partnerships
The center is governed by a scientific advisory board with representatives from major research institutions, including Harvard Medical School, Massachusetts General Hospital, and the Broad Institute. Regular peer review ensures that the center maintains the highest standards of quality and scientific integrity.
Quality Metrics
The HBTRC maintains rigorous quality metrics for all tissue samples:
- Postmortem Interval (PMI): Average <12 hours, with target <6 hours for optimal molecular studies
- Tissue Quality: RNA integrity numbers (RIN) >7.0 for 95% of frozen specimens
- Documentation: Complete clinical records for 100% of cases
- Neuropathology: Comprehensive assessment by board-certified neuropathologists
- Storage: -80°C frozen storage with continuous temperature monitoring
- Traceability: Complete chain-of-custody documentation for all samples
Sample Types Available
Researchers can request various tissue preparations:
- Fresh frozen: Unfixed, flash-frozen tissue for molecular studies
- Formalin-fixed paraffin-embedded (FFPE): Tissue blocks and sections for histology
- Fixed frozen: Cryoprotected tissue for immunohistochemistry
- Isolated nuclei: Fresh nuclei for single-cell sequencing
- RNA/DNA: Extracted nucleic acids from characterized cases
- Plasma/CSF: Paired cerebrospinal fluid and plasma samples
Future Directions
The HBTRC is implementing several initiatives to enhance its contribution to neurodegenerative disease research:
Enhanced Clinical Characterization: Integrating longitudinal clinical data from clinicaltrials.gov and biomarker studies
Multi-omics Integration: Adding proteomic and metabolomic data to existing genomic resources
Stem Cell Repository: Creating a collection of induced pluripotent stem cell lines from well-characterized donors
Data Sharing Portal: Developing a public database for tissue availability and case metadata
Standardization Efforts: Promoting harmonization of brain bank protocols internationallySee Also
- [Brain Banks](/topics/brain-banks)
- [Alzheimer's Disease Research](/diseases/alzheimers-disease)
- [Parkinson's Disease Research](/diseases/parkinsons-disease)](/proteins/parkin)
- [McLean Hospital](/institutions/mclean-hospital)](/institutions)
- [Harvard Medical School](/institutions/harvard-med)
External Links
- [HBTRC Website](https://www.brainbank.mclean.org)
- [NIH NIMH](https://www.nimh.nih.gov)
- [McLean Hospital](https://www.mcleanhospital.org)
References
[HBTRC Annual Report](https://www.brainbank.mclean.org)
[Braak H et al, Staging of brain pathology related to sporadic Parkinson's disease (2003)](https://pubmed.ncbi.nlm.nih.gov/12584368/)
[Jellinger KA et al, Staging of the pathology of Parkinson's disease (2004)](https://pubmed.ncbi.nlm.nih.gov/15567490/)
[Beach TG et al, Unified staging system for Lewy body disorders (2009)](https://pubmed.ncbi.nlm.nih.gov/19332113/)
[Hyman BT et al, National Institute on Aging-Alzheimer's Association guidelines (2012)](https://pubmed.ncbi.nlm.nih.gov/22436740/)
[Montine TJ et al, NIA-AA guidelines for neuropathologic assessment (2012)](https://pubmed.ncbi.nlm.nih.gov/22436744/)
[Vonsattel JPG et al, Neuropathology of Alzheimer's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32060967/)
[Dickson DW et al, Neuropathology of Alzheimer's disease (2018)](https://pubmed.ncbi.nlm.nih.gov/29538653/)
[ Thal DR et al, Phases of Aβ-deposition in the human brain (2002)](https://pubmed.ncbi.nlm.nih.gov/12393245/)
[Alafuzoff I et al, Staging of Alzheimer-type pathology (2008)](https://pubmed.ncbi.nlm.nih.gov/18331440/)
[Braak H et al, Neuropathological staging of Alzheimer-related changes (2006)](https://pubmed.ncbi.nlm.nih.gov/16545497/)
[Walker LC et al, Alzheimer disease: one disease or many? (2015)](https://pubmed.ncbi.nlm.nih.gov/26192641/)
[Nelson PT et al, Correlation of Alzheimer disease neuropathologic changes with cognitive status (2012)](https://pubmed.ncbi.nlm.nih.gov/22403040/)
[Bennett DA et al, Neuropathology of older persons without cognitive impairment (2006)](https://pubmed.ncbi.nlm.nih.gov/16641938/)
[Jagust WJ et al, PET imaging of amyloid in the brain (2013)](https://pubmed.ncbi.nlm.nih.gov/24014567/)
[Jack CR et al, Hypothetical model of dynamic biomarkers of Alzheimer's disease (2013)](https://pubmed.ncbi.nlm.nih.gov/23558441/)
[Sperling RA et al, Toward defining the preclinical stages of Alzheimer's disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21304398/)
[Albert MS et al, The diagnosis of mild cognitive impairment (2011)](https://pubmed.ncbi.nlm.nih.gov/21304400/)
[McKhann GM et al, Clinical diagnosis of Alzheimer's disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21304401/)
[Knopman DS et al, Neuropathology of dementia (2021)](https://pubmed.ncbi.nlm.nih.gov/33784452/)
[Robinson JL et al, Neurodegenerative disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34545678/)