MRC Brain Banks: Joint Application to Underpin Neuroscience Research
Lead Research Organisation:
University of Edinburgh
Department Name: Centre for Clinical Brain Sciences
Abstract
This application plans to support research into the causes and potential treatment of a range of diseases affecting the
brain, some of which have been identified as priorities for research, such as dementia. The UK has a network of
established Brain Banks that provide human tissue samples to a wide range of researchers. Human tissue samples have
allowed a better understanding of the mechanisms operating in these complex disorders and have already aided the
development of treatments for Alzheimer's disease and Parkinson's disease.
This application will support four Brain Banks in Edinburgh, London, Newcastle and Oxford. These banks each have areas
of particular interest, Parkinson's disease, Alzheimer's disease and motor neurone disease. However, in addition to the
collection of tissues samples from patients with brain disorders, it is also essential to collect normal tissue samples for use
as controls in research. Two of the Banks have a major focus in this area, so this application will support the collection of
both disease and normal tissue samples.
The banks will support scientific research by providing human tissue samples in an efficient and cost effective manner,
while ensuring the samples provided are of the high quality required by researchers. The banks have worked to improve
their efficiency, reducing the time required to provide the samples to researchers. Details of the samples available in each
of the banks are included in a database, which is accessible through the internet. This allows researchers to see what
samples are available and how to request these samples for their research in an easy way that will save time and speed up
progress.
All four Brain Banks in this application have approval form an Ethics Committee, to ensure that their working practices meet
nationally agreed standards that apply to work with human tissue samples. The work of each Bank is overseen by a local
steering committee that includes members of the public and ethics experts as well as scientists and pathologists. Brain
Banking is expensive, but the operating costs of these four banks are far less than their equivalents in Europe and in the
USA.
The challenges of developing treatments for complex diseases such as Alzheimer's disease and Parkinson's disease are
considerable, but the Brain Banks in this application will play an important role in underpinning the scientific research in these
national priority areas.
brain, some of which have been identified as priorities for research, such as dementia. The UK has a network of
established Brain Banks that provide human tissue samples to a wide range of researchers. Human tissue samples have
allowed a better understanding of the mechanisms operating in these complex disorders and have already aided the
development of treatments for Alzheimer's disease and Parkinson's disease.
This application will support four Brain Banks in Edinburgh, London, Newcastle and Oxford. These banks each have areas
of particular interest, Parkinson's disease, Alzheimer's disease and motor neurone disease. However, in addition to the
collection of tissues samples from patients with brain disorders, it is also essential to collect normal tissue samples for use
as controls in research. Two of the Banks have a major focus in this area, so this application will support the collection of
both disease and normal tissue samples.
The banks will support scientific research by providing human tissue samples in an efficient and cost effective manner,
while ensuring the samples provided are of the high quality required by researchers. The banks have worked to improve
their efficiency, reducing the time required to provide the samples to researchers. Details of the samples available in each
of the banks are included in a database, which is accessible through the internet. This allows researchers to see what
samples are available and how to request these samples for their research in an easy way that will save time and speed up
progress.
All four Brain Banks in this application have approval form an Ethics Committee, to ensure that their working practices meet
nationally agreed standards that apply to work with human tissue samples. The work of each Bank is overseen by a local
steering committee that includes members of the public and ethics experts as well as scientists and pathologists. Brain
Banking is expensive, but the operating costs of these four banks are far less than their equivalents in Europe and in the
USA.
The challenges of developing treatments for complex diseases such as Alzheimer's disease and Parkinson's disease are
considerable, but the Brain Banks in this application will play an important role in underpinning the scientific research in these
national priority areas.
Technical Summary
This joint application from the MRC Brain Banks in Edinburgh, London, Newcastle and Oxford is submitted in accordance
with the wishes of the MRC Neuroscience and Mental Health Board (NMHB). After the last funding round for the MRC
Brain Banks in 2011, NMHB indicated that a future joint application would be preferred and that the applicants should
demonstrate progress in efficiency and improving standards of work in accordance with an agreed set of metrics. This
application fulfils this request, and aims to underpin neuroscience research in the UK by providing high-quality human brain
tissue samples and data in the formats required by researchers in both academic and industrial settings. The four banks in
this application together cover the collection of human tissue samples from a range of major neurological diseases, and
normal tissue samples to act as controls. This provides an invaluable resource to underpin neuroscience research in UK,
particularly in recently identified priority areas such as dementia.
The banks have demonstrated in this application that they can work to the standards set in the metrics agreed with the
NMHB, and have improved their efficiency of operations. The banks already support a number of major researchers in
academia and industry in UK and overseas, including several who are currently funded by MRC. The provision of high
quality tissue samples and accompanying data is essential for the success of these projects; the MRC brain banks
constitute a critical infrastructure for this research.
In order to develop this important work further, funding for a 5 year period is requested; earlier funding awards for periods
of 2 years has not been conducive to long term planning and strategy. The costs of brain banking in the UK compare very
favourably with those in Europe and in the USA; over the next 5 years the banks will continue to work to improve efficiency
of operation and to operate a cost recovery programme.
with the wishes of the MRC Neuroscience and Mental Health Board (NMHB). After the last funding round for the MRC
Brain Banks in 2011, NMHB indicated that a future joint application would be preferred and that the applicants should
demonstrate progress in efficiency and improving standards of work in accordance with an agreed set of metrics. This
application fulfils this request, and aims to underpin neuroscience research in the UK by providing high-quality human brain
tissue samples and data in the formats required by researchers in both academic and industrial settings. The four banks in
this application together cover the collection of human tissue samples from a range of major neurological diseases, and
normal tissue samples to act as controls. This provides an invaluable resource to underpin neuroscience research in UK,
particularly in recently identified priority areas such as dementia.
The banks have demonstrated in this application that they can work to the standards set in the metrics agreed with the
NMHB, and have improved their efficiency of operations. The banks already support a number of major researchers in
academia and industry in UK and overseas, including several who are currently funded by MRC. The provision of high
quality tissue samples and accompanying data is essential for the success of these projects; the MRC brain banks
constitute a critical infrastructure for this research.
In order to develop this important work further, funding for a 5 year period is requested; earlier funding awards for periods
of 2 years has not been conducive to long term planning and strategy. The costs of brain banking in the UK compare very
favourably with those in Europe and in the USA; over the next 5 years the banks will continue to work to improve efficiency
of operation and to operate a cost recovery programme.
Planned Impact
The activities of the brain banks will be of major significance to neuroscience researchers in the UK and the banks plan to
capitalise upon this by promoting the availability of their tissue samples during the course of this grant, primarily by the
MRC database, which will give details of all samples currently available, including control samples. This promotion will not
be confined to academic researchers, but also through the Association of British Pharmaceutical Industries the applicants
will promote the availability of the tissue samples in their banks and will engage with both academic and industrial
researchers to help provide the samples they require.
The brain banks already supply tissue samples to commercial companies for their research and development purposes and
it is planned to continue and develop these contacts within an appropriate framework.
The applicants are involved in a number of local, national and international committees and bodies that relate to research.
Policymakers within both government (DH) and non-governmental organisations and regulators (e.g. the Human Tissue
Authority) will benefit from information arising from the use of human brain tissue samples and also from the general
promotion of brain donation in neuroscience research.
The applicants have previously engaged with museums (including the Wellcome Trust museum) and charities including the
Alzheimer's Society, Alzheimer's Research UK, the Multiple Sclerosis Society and Parkinson's UK to provide expert advice
on brain banking. The applicants also work within the committee structure of these charities to advise on their research
activities, particularly those that might involve the collection and use of human tissue samples.
The wider public is likely to benefit from this planned research, particularly if the tissue samples provided result in improved
diagnosis or treatment for patients with neurodegenerative disorders. Furthermore, the promotion of brain banking and the
value of brain donation for research will help raise public awareness of the challenges of dementia and neurodegenerative
diseases, and help make individuals take an informed choice on this complex matter.
It is likely that the government may benefit from this research, particularly in respect to the activities of the Ministerial Action
Group on Dementia Research and the Prime Minister's Challenge on dementia, within which brain banking is
acknowledged as an essential requirement to support researchers in this field. The support requested in this application
will be of wider benefit to these government initiatives and the research arising from this work, supported by other
government funded bodies including NIHR.
Finally, MRC is likely to benefit from this research, since the applicants already provide large numbers of tissue samples to
researchers such as Professor John Hardy, UCL, who are in receipt of significant funding from MRC to undertake research
projects that are critically dependent on a continuous supply of high quality tissue samples that will be collected and made
available during the course of this proposal.
capitalise upon this by promoting the availability of their tissue samples during the course of this grant, primarily by the
MRC database, which will give details of all samples currently available, including control samples. This promotion will not
be confined to academic researchers, but also through the Association of British Pharmaceutical Industries the applicants
will promote the availability of the tissue samples in their banks and will engage with both academic and industrial
researchers to help provide the samples they require.
The brain banks already supply tissue samples to commercial companies for their research and development purposes and
it is planned to continue and develop these contacts within an appropriate framework.
The applicants are involved in a number of local, national and international committees and bodies that relate to research.
Policymakers within both government (DH) and non-governmental organisations and regulators (e.g. the Human Tissue
Authority) will benefit from information arising from the use of human brain tissue samples and also from the general
promotion of brain donation in neuroscience research.
The applicants have previously engaged with museums (including the Wellcome Trust museum) and charities including the
Alzheimer's Society, Alzheimer's Research UK, the Multiple Sclerosis Society and Parkinson's UK to provide expert advice
on brain banking. The applicants also work within the committee structure of these charities to advise on their research
activities, particularly those that might involve the collection and use of human tissue samples.
The wider public is likely to benefit from this planned research, particularly if the tissue samples provided result in improved
diagnosis or treatment for patients with neurodegenerative disorders. Furthermore, the promotion of brain banking and the
value of brain donation for research will help raise public awareness of the challenges of dementia and neurodegenerative
diseases, and help make individuals take an informed choice on this complex matter.
It is likely that the government may benefit from this research, particularly in respect to the activities of the Ministerial Action
Group on Dementia Research and the Prime Minister's Challenge on dementia, within which brain banking is
acknowledged as an essential requirement to support researchers in this field. The support requested in this application
will be of wider benefit to these government initiatives and the research arising from this work, supported by other
government funded bodies including NIHR.
Finally, MRC is likely to benefit from this research, since the applicants already provide large numbers of tissue samples to
researchers such as Professor John Hardy, UCL, who are in receipt of significant funding from MRC to undertake research
projects that are critically dependent on a continuous supply of high quality tissue samples that will be collected and made
available during the course of this proposal.
People |
ORCID iD |
Colin Smith (Principal Investigator) | |
Donald MacIntyre (Researcher) |
Publications
Adams HH
(2016)
Novel genetic loci underlying human intracranial volume identified through genome-wide association.
in Nature neuroscience
Alafuzoff I
(2015)
Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium.
in Journal of neural transmission (Vienna, Austria : 1996)
Alfieri A
(2022)
Nox2 underpins microvascular inflammation and vascular contributions to cognitive decline.
in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Askew KE
(2024)
Inhibiting CSF1R alleviates cerebrovascular white matter disease and cognitive impairment.
in Glia
Assar H
(2015)
A case of variably protease-sensitive prionopathy treated with doxycyclin.
in Journal of neurology, neurosurgery, and psychiatry
Attems J
(2021)
Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study.
in Acta neuropathologica
Bailey EL
(2014)
Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.
in Neuropathology and applied neurobiology
Banerjee P
(2022)
NLRP3 inflammasome as a key molecular target underlying cognitive resilience in amyotrophic lateral sclerosis.
in The Journal of pathology
Banerjee P
(2023)
Cell-autonomous immune dysfunction driven by disrupted autophagy in C9orf72 -ALS iPSC-derived microglia contributes to neurodegeneration
in Science Advances
Barton SK
(2021)
Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis.
in Frontiers in neuroscience
Bishop MT
(2013)
Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt-Jakob disease.
in Brain : a journal of neurology
Bougard D
(2018)
Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification.
in Emerging infectious diseases
Boyle A
(2020)
No Adaptation of the Prion Strain in a Heterozygous Case of Variant Creutzfeldt-Jakob Disease.
in Emerging infectious diseases
Chelban V
(2017)
Analysis of the prion protein gene in multiple system atrophy.
in Neurobiology of aging
Choi YP
(2014)
Uptake and degradation of protease-sensitive and -resistant forms of abnormal human prion protein aggregates by human astrocytes.
in The American journal of pathology
Colom-Cadena M
(2017)
Synaptic phosphorylated a-synuclein in dementia with Lewy bodies.
in Brain : a journal of neurology
Cruchaga C
(2014)
Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.
in Nature
Curran O
(2020)
A single-synapse resolution survey of PSD95-positive synapses in twenty human brain regions
in European Journal of Neuroscience
De Sousa P
(2018)
Renewed assessment of the risk of emergent advanced cell therapies to transmit neuroproteinopathies
in Acta Neuropathologica
Diack AB
(2017)
Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case.
in Emerging infectious diseases
Diack AB
(2014)
Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties.
in Emerging infectious diseases
Diack AB
(2014)
Variant CJD. 18 years of research and surveillance.
in Prion
Dillenburg A
(2018)
Activin receptors regulate the oligodendrocyte lineage in health and disease.
in Acta neuropathologica
Dorward DA
(2021)
Tissue-Specific Immunopathology in Fatal COVID-19.
in American journal of respiratory and critical care medicine
Douet JY
(2017)
Distribution and Quantitative Estimates of Variant Creutzfeldt-Jakob Disease Prions in Tissues of Clinical and Asymptomatic Patients.
in Emerging infectious diseases
Falcão AM
(2018)
Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis.
in Nature medicine
Ferrari R
(2014)
Assessment of common variability and expression quantitative trait loci for genome-wide associations for progressive supranuclear palsy
in Neurobiology of Aging
Forabosco P
(2013)
Insights into TREM2 biology by network analysis of human brain gene expression data.
in Neurobiology of aging
Franke B
(2016)
Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.
in Nature neuroscience
Gadd DA
(2021)
Epigenetic predictors of lifestyle traits applied to the blood and brain.
in Brain communications
Geng L
(2020)
Nox2 dependent redox-regulation of microglial response to amyloid-ß stimulation and microgliosis in aging.
in Scientific reports
Graham LC
(2017)
Proteomic profiling of neuronal mitochondria reveals modulators of synaptic architecture.
in Molecular neurodegeneration
Green AJE
(2018)
Prion protein amplification techniques.
in Handbook of clinical neurology
Gregory J
(2020)
Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis
in Neuropathology and Applied Neurobiology
Gregory JM
(2020)
Dysregulation of AMPA receptor subunit expression in sporadic ALS post-mortem brain.
in The Journal of pathology
Gregory JM
(2017)
Clusterin protects neurons against intracellular proteotoxicity.
in Acta neuropathologica communications
Gregory JM
(2020)
Neuronal clusterin expression is associated with cognitive protection in amyotrophic lateral sclerosis.
in Neuropathology and applied neurobiology
Gregory JM
(2020)
Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS.
in Journal of neurology, neurosurgery, and psychiatry
Guelfi S
(2019)
Transcriptomic and genetic analyses reveal potential causal drivers for intractable partial epilepsy.
in Brain : a journal of neurology
Head MW
(2013)
Variably protease-sensitive prionopathy in the UK: a retrospective review 1991-2008.
in Brain : a journal of neurology
Henstridge C
(2017)
Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis
in Acta Neuropathologica
Henstridge CM
(2015)
Post-mortem brain analyses of the Lothian Birth Cohort 1936: extending lifetime cognitive and brain phenotyping to the level of the synapse.
in Acta neuropathologica communications
Hesse R
(2019)
Comparative profiling of the synaptic proteome from Alzheimer's disease patients with focus on the APOE genotype.
in Acta neuropathologica communications
Hibar DP
(2017)
Novel genetic loci associated with hippocampal volume.
in Nature communications
Hibar DP
(2015)
Common genetic variants influence human subcortical brain structures.
in Nature
Holland PR
(2015)
Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease.
in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Humphreys CA
(2019)
A protocol for precise comparisons of small vessel disease lesions between ex vivo magnetic resonance imaging and histopathology.
in International journal of stroke : official journal of the International Stroke Society
Jackson RJ
(2019)
Clusterin accumulates in synapses in Alzheimer's disease and is increased in apolipoprotein E4 carriers.
in Brain communications
Description | Capital Investment in Human Tissue Banking and Linked Data, in Partnership with Charities |
Amount | £598,000 (GBP) |
Funding ID | MR/RO14140/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 03/2021 |
Description | Maximising the value of MRC Brain Banks: high-throughput genomic studies to enrich data available to the research community |
Amount | £1,670,000 (GBP) |
Funding ID | MC_PC_13044 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2013 |
End | 10/2016 |
Description | Neuro-Inflammation after Cerebral Haemorrhage in Edinburgh (NICHE) |
Amount | £449,482 (GBP) |
Funding ID | TSA PPA 2017-01 |
Organisation | Stroke Association |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2018 |
End | 03/2022 |
Title | Post Mortem imaging |
Description | We have developed a novel approach to imaging of post mortem brain samples allowing us to directly correlate microscopic/molecular changes with neuroradiological poarameters, such as white matter hyperintensities. This allows us to directly study the molecular and cellular changes that underpin radiological changes and assess how they contribute to disease progression. |
Type Of Material | Biological samples |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | We are aware of other international brain banks who are looking to implement our protocol. |
URL | http://journals.sagepub.com/doi/abs/10.1177/1747493018799962?url_ver=Z39.88-2003&rfr_id=ori:rid:cros... |
Title | MRC Brain Bank database |
Description | This is a national brain bank database allowing neuroscience researchers an east access point to assess availability of human brain tissues throughout the UK |
Type Of Material | Database/Collection of data |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Standardised approach to basic neuropathological data stored across UK Brain Bank Network |
URL | https://brainbanknetwork.cse.bris.ac.uk |
Description | Key provider of human tissue to genome profiling group |
Organisation | University College London |
Department | Institute of Neurology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Supply of age matched control human brain tissue |
Collaborator Contribution | Has helped develop a more robust standardised sampling protocol for brain examination and storage. |
Impact | A number of publications have been submitted. |
Start Year | 2008 |
Description | National awards ceremony |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | The Stroke Association Research awards event 2nd May 2018 at Guildhall London, at which the award for the small vessel disease brain bank was presented. The audience comprised patients, carers, academics and media groups. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.ed.ac.uk/clinical-brain-sciences/news/news-jan-jun-2018/stroke-assoc-awardees-2018 |
Description | Radio Scotland interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Radio interview as part of a panel discussing the ethics of brain donation for biomedical research |
Year(s) Of Engagement Activity | 2017 |
Description | Specialist presentation at British Neuroscience Association Festival of Neuroscience 2019 (Dublin) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | As part of a session on the ageing brain I provided a presentation outlining the MRC brain bank facilities, particularly focusing on the website and database. |
Year(s) Of Engagement Activity | 2019 |
URL | https://meetings.bna.org.uk/bna2019/ |