The Mayo Clinic Brain Bank, headquartered at Mayo Clinic Jacksonville in Florida, is one of the world's most comprehensive brain tissue repositories for neurodegenerative disease research. The brain bank specializes in collecting, preserving, and distributing postmortem brain tissue from well-characterized patients with Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Lewy body disease, and other neurodegenerative conditions. The repository supports both basic science and clinical translation research efforts globally.
Location: Jacksonville, Florida, USA
Type: Brain Tissue Repository
Founded: 1990s
Affiliation: Mayo Clinic
Focus: AD, PD, FTD, LBD, ALS, CTE
¶ History and Development
The Mayo Clinic Brain Bank was established in the 1990s as part of Mayo Clinic's expanding neurodegenerative disease research program in Jacksonville, Florida. Under the leadership of renowned neuropathologist Dennis W. Dickson, MD, the brain bank grew to become one of the largest and most well-characterized brain tissue collections in the world for neurodegenerative research.
The brain bank benefited from the establishment of the Mayo Clinic Alzheimer's Disease Research Center and the movement disorders research program, which provided a steady stream of clinically well-characterized donors. Over the decades, the repository has accumulated thousands of brain specimens, each with comprehensive clinical, pathological, and demographic data.
The Mayo Clinic Brain Bank maintains particular strength in the following neurodegenerative conditions:
| Disease Category |
Focus Areas |
| Alzheimer's Disease |
Typical and atypical AD, early-onset AD, Down syndrome-associated AD |
| Parkinson's Disease |
Classic PD, PD with dementia, incidental Lewy body disease |
| Frontotemporal Dementia |
Behavioral variant FTD, semantic variant PPA, nonfluent variant PPA |
| Lewy Body Disease |
Dementia with Lewy bodies, Parkinson's disease dementia |
| Amyotrophic Lateral Sclerosis |
Sporadic and familial ALS, ALS-FTD spectrum |
| Atypical Parkinsonian Syndromes |
Progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy |
| Chronic Traumatic Encephalopathy |
Sports-related CTE, traumatic brain injury-associated neurodegeneration |
The repository provides researchers with:
- Frozen tissue: Fresh-frozen brain regions for molecular and biochemical studies
- Formalin-fixed tissue: Paraffin-embedded blocks for histology and immunohistochemistry
- Fresh tissue: Refrigerated tissue for cell culture and molecular biology
- Tissue sections: Mounted slides for in situ hybridization and staining
- DNA/RNA: Extracted genetic material from brain tissue
The Mayo Clinic Brain Bank has been instrumental in advancing understanding of neurodegenerative diseases. Key contributions include:
The brain bank has been essential for validating antemortem biomarkers, including PET ligands for amyloid and tau pathology. Studies validating amyloid PET tracers and tau PET ligands have relied on autopsy confirmation from brain bank specimens.
Brain bank tissue has supported numerous genetic investigations, including:
- APOE allele frequency studies in AD
- MAPT mutations in FTD
- GRN haploinsufficiency in FTD
- C9orf72 repeat expansion in ALS-FTD
- LRRK2 mutations in PD
Mayo Clinic neuropathologists have used the brain bank to define diagnostic criteria for numerous conditions, including:
The brain bank has provided tissue for biomarker studies in numerous clinical trials, including:
- Aducanumab (Aβ antibody) trials
- Anti-tau immunotherapy studies
- LRRK2 inhibitor trials
- Alpha-synuclein-targeted therapies
- Professor of Pathology and Neurology, Mayo Clinic College of Medicine
- Director of the Mayo Clinic Brain Bank
- Internationally recognized expert in neurodegenerative disease neuropathology
- Key publications on tauopathies, synucleinopathies, and TDP-43 proteinopathies
- Associate Professor of Neuroscience, Mayo Clinic Florida
- Deputy Director, Mayo Clinic Brain Bank
- Expert in Alzheimer disease neuropathology and biomarker development
- Notable work on hippocampal sclerosis and LATE-NC
- Professor of Neurology, Mayo Clinic
- Expert on FTD and atypical parkinsonism
- Clinical-pathological correlation studies
- Professor of Neuroscience, Mayo Clinic Florida
- Expert on genetic causes of FTD and PD
- Led discovery of C9orf72 repeat expansion
- Professor of Neurology, Mayo Clinic
- Expert on Lewy body disease and DLB
- Biomarker development for Lewy body disorders
- Professor of Psychiatry and Psychology, Mayo Clinic
- Expert on DLB vs. AD differentiation
- Clinical and pathological correlation studies
¶ Stephen D. Weigand, MS
- Biostatistician, Mayo Clinic
- Statistical analysis of neuropathological data
- Development of staging schemes
¶ Tissue Processing and Quality Assurance
The Mayo Clinic Brain Bank follows rigorous collection protocols to ensure tissue quality:
- Rapid Autopsy Program: Mean postmortem interval (PMI) of 3-6 hours for optimal tissue preservation
- Systematic Brain Dissection: Standardized regional sampling across 30+ brain regions
- Clinical Correlation: All cases have comprehensive antemortem clinical documentation
- Neuropathological Assessment: Complete evaluation using standardized diagnostic criteria
- Freezer Monitoring: Continuous temperature monitoring with alarm systems
- Tissue Banking: Multiple aliquots stored at -80°C for molecular studies
- Histology Quality: H&E staining and special stains performed on all cases
- Molecular Verification: DNA/RNA quality assessed before distribution
Each specimen includes:
- Complete neuropathological diagnosis
- Braak staging for tau and amyloid-beta
- Lewy body distribution (Lewy Body Disease staging)
- Detailed clinical summary
- Family history information
- Medication history
Researchers can access tissue from the Mayo Clinic Brain Bank through several pathways:
- Collaborative studies: Formal research collaborations with Mayo Clinic investigators
- Tissue request: Official tissue request through the Mayo Clinic biorepository
- NIH-supported projects: Projects funded by NIA, NINDS, and other federal agencies
- Industry partnerships: Pharmaceutical company research agreements
All requests require:
- Scientific proposal review
- Institutional IRB approval
- Material transfer agreement
- Appropriate biosafety certification
¶ Notable Publications and Discoveries
¶ Landmark Publications
The Mayo Clinic Brain Bank has contributed to numerous landmark publications:
-
LATE-NC Discovery: Definition and characterization of Limbic-predominant Age-related TDP-43 Encephalopathy Neuropathological Change (LATE-NC), a newly recognized pathologic entity affecting up to 20% of elderly individuals[@murray2019].
-
Tau Staging: Development of the tau staging scheme for Alzheimer disease, showing predictable progression of neurofibrillary degeneration through specific brain regions[@cook2017].
-
PART Recognition: Definition of Primary Age-related Tauopathy (PART), a tauopathy distinct from AD that accounts for many cases of hippocampal sclerosis in the elderly.
-
C9orf72 Discovery: Key role in identifying the hexanucleotide repeat expansion in C9orf72 as the most common genetic cause of familial ALS and FTD.
-
TDP-43 Pathology: Pioneering work on TDP-43 proteinopathies, including ALS, FTD, and LATE-NC[@dickson2020].
-
Lewy Body Staging: Development of criteria for staging Lewy body distribution and correlation with clinical symptoms.
Recent research using brain bank tissue has focused on:
- Biomarker Validation: Correlation of antemortem PET imaging with postmortem pathology
- Genetic Risk Factors: Study of APOE, TMEM106B, and other risk genes
- Protein Propagation: Mechanisms of pathological protein spreading in neurodegenerative diseases
- Cell-Type Specific Vulnerability: Understanding why specific neurons are vulnerable in different diseases
- Spatial Transcriptomics: Gene expression mapping across brain regions
¶ Training and Education
The brain bank supports training and education:
- Fellowship Training: Neuropathology fellows receive hands-on training
- Visiting Scientists: International researchers conduct studies at Mayo
- Workshops: Annual hands-on neuropathology workshops
- Online Resources: Virtual slide sets for teaching
- Total specimens: Thousands of brains representing dozens of neurodegenerative conditions
- Annual distributions: Hundreds of tissue samples distributed to researchers worldwide
- Clinical follow-up: Extensive longitudinal clinical data available for most donors
- Neuropathological confirmation: All cases include comprehensive neuropathological assessment using standardized criteria
- Average PMI: 4.5 hours (optimal for molecular studies)
- Brain regions sampled: 30+ regions per case
- Cases with genetic data: Over 1,000 whole genome sequences available
The Mayo Clinic Brain Bank supports research on numerous neurodegenerative diseases documented in this wiki:
Key proteins studied using brain bank tissue:
Key genes studied using brain bank tissue:
The brain bank maintains one of the largest well-characterized AD tissue collections, including:
- Typical late-onset AD
- Early-onset familial AD (APP, PSEN1, PSEN2 mutations)
- Atypical AD (posterior cortical atrophy, logopenic variant PPA)
- Down syndrome-associated AD
- Mixed pathology cases (AD + LBD, AD + vascular pathology)
The PD collection includes:
The FTD collection includes:
- Behavioral variant FTD
- Semantic variant primary progressive aphasia
- Nonfluent/agrammatic variant PPA
- FTD with motor neuron disease
- Corticobasal degeneration
¶ Quality Metrics and Standards
The Mayo Clinic Brain Bank maintains:
- NIH-funded biorepository certification
- IRB oversight for human tissue collection
- Biosafety Level 2 certification
- Material Transfer Agreement compliance
| Metric |
Target |
Actual |
| Average PMI |
<6 hours |
4.5 hours |
| RNA Integrity Number |
>7.0 |
7.8 average |
| DNA Quality |
High molecular weight |
260/280 >1.8 |
| Fixation Quality |
<48 hours |
24-36 hours |
- National Alzheimer's Coordinating Center (NACC): Contributing to the large-scale database of neuropathological data
- Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD): Multi-omics analysis of brain tissue
- International Frontotemporal Dementia Genomics Consortium: Genetic and functional studies
- Lewy Body Dementia Association: Biomarker validation studies
The brain bank collaborates with pharmaceutical companies for:
- Clinical trial biomarker studies
- Target validation
- Drug mechanism of action studies
- Patient stratification markers
The Mayo Clinic Brain Bank continues to expand its contributions to neurodegenerative disease research:
- Single-Cell Sequencing: Characterizing cell-type specific changes
- Spatial Transcriptomics: Mapping gene expression across brain regions
- Proteomics: Large-scale protein analysis of disease-specific changes
- iPSC Derivation: Creating induced pluripotent stem cells from brain bank tissue
- Digital Pathology: Integration of whole slide imaging with molecular data
- Multi-Omics Integration: Combining genomics, transcriptomics, proteomics, and metabolomics data
One of the unique strengths of the Mayo Clinic Brain Bank is the availability of extensive longitudinal clinical data for most donors:
- Cognitive Assessments: Annual MMSE, MoCA, and neuropsychological testing batteries
- Motor Assessments: UPDRS for PD patients, ALSFRS-R for ALS patients
- Clinical Diagnoses: Multiple clinical evaluations over disease course
- Imaging Data: MRI and CT scans available for correlation
- Treatment History: Medication and intervention history documented
- Family History: Comprehensive family history of neurological disease
The brain bank maintains a registry of all donors:
- Contact Information: Next of kin contacts for follow-up
- Consent Documentation: Comprehensive consent for research use
- Tissue Utilization Tracking: Records of all tissue distributions
- Publication Tracking: Links to publications using brain bank tissue
The Mayo Clinic Brain Bank provides comprehensive neuropathological evaluation:
-
Standard Neuropathological Assessment
- Gross examination and brain weight
- Regional sampling for histology
- H&E staining and special stains
- Immunohistochemistry for key proteins
-
Specialized Stains and Immunohistochemistry
- Amyloid-beta (4G8, 6E10)
- Phospho-tau (AT8, PHF-1)
- Alpha-synuclein (LB509, EP1536Y)
- TDP-43 (phospho and total)
- FUS, p62, and other proteins
-
Quantitative Assessment
- Braak tau stage
- Thal amyloid phase
- CERAD neuritic plaque score
- Lewy body distribution
- Vascular pathology scoring
¶ Funding and Support
The Mayo Clinic Brain Bank is supported by:
- National Institutes of Health (NIH): NIA and NINDS grants
- Mayo Clinic Foundation: Institutional support
- Alzheimer's Association: Research grants
- Michael J. Fox Foundation: Parkinson's disease research
- ALS Association: ALS tissue collection
- Private Donors: Charitable contributions
- Dickson et al., Neuropathology of neurodegenerative diseases: a practical guide (2020)
- Murray et al., LATE-NC: A new and common neuropathologic finding (2019)
- Josephs et al., Progressive supranuclear palsy: clinicopathologic concepts and diagnostic challenges (2014)
- Cook et al., Staging of Alzheimer's disease-related neurofibrillary degeneration (2017)
- Petersen et al., Mayo Clinic Alzheimer's Disease Research Center: 25 years of contributions to understanding AD (2018)
- Dickson & Wetter, Tauopathies: Classification and clinical approach to therapy (2021)
- Murray et al., Alzheimer disease neuropathology in the Mayo Clinic Brain Bank (2022)
- Rademakers et al., Common inversion at 17q21.31 in association with tauopathies (2012)
- White et al., Role of tau as a biomarker for neurodegenerative disease (2013)
- Daud et al., TDP-43 pathology in neurodegenerative disease (2012)
- Ferman et al., Dementia with Lewy bodies: importance of temporal lobe atrophy (2016)
- Josephs et al., Updated TBI-CTE diagnostic criteria for chronic traumatic encephalopathy (2017)
- Murray et al., Neuropathologically defined subtypes of Alzheimer disease (2013)
- Dickson et al., Neuropathology of Lewy body diseases (2018)
- Kantarci et al., Tau PET imaging with flortaucipir in aging and Alzheimer disease (2020)
- Whitwell et al., Neuroimaging signatures of progressive supranuclear palsy (2017)
- Adamczak et al., In vivo tau PET imaging in Alzheimer's disease (2020)
- Schneider et al., Mixed pathology and memory decline (2019)
- Spinelli et al., TDP-43 in the hippocampus in aging and AD (2019)
- Toomey et al., TREM2 deficiency exacerbates tau pathology (2019)