MRC Brain Banks: Joint Application to Underpin Neuroscience Research
Lead Research Organisation:
King's College London
Department Name: Clinical Neuroscience
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 in keeping with MRC
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 in keeping with MRC
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.
Publications
Kun-Rodrigues C
(2017)
Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies.
in Neurobiology of aging
Kun-Rodrigues C
(2019)
A comprehensive screening of copy number variability in dementia with Lewy bodies.
in Neurobiology of aging
Kurbatskaya K
(2016)
Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer's disease brain.
in Acta neuropathologica communications
Lantero Rodriguez J
(2020)
Plasma p-tau181 accurately predicts Alzheimer's disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline.
in Acta neuropathologica
Lau DHW
(2020)
Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer's disease brain.
in Neurobiology of disease
Lee YB
(2021)
C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity.
in Human molecular genetics
Lee YB
(2013)
Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.
in Cell reports
Lee YB
(2017)
C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity.
in Human molecular genetics
Lee YB
(2021)
Cytoplasmic TDP-43 is involved in cell fate during stress recovery.
in Human molecular genetics
Lunnon K
(2016)
Erratum to: Variation in 5-hydroxymethylcytosine across human cortex and cerebellum.
in Genome biology
Lunnon K
(2016)
Variation in 5-hydroxymethylcytosine across human cortex and cerebellum.
in Genome biology
Ly H
(2021)
The association of circulating amylin with ß-amyloid in familial Alzheimer's disease.
in Alzheimer's & dementia (New York, N. Y.)
Marzi SJ
(2018)
A histone acetylome-wide association study of Alzheimer's disease identifies disease-associated H3K27ac differences in the entorhinal cortex.
in Nature neuroscience
Marzi SJ
(2016)
Tissue-specific patterns of allelically-skewed DNA methylation.
in Epigenetics
McAleese KE
(2021)
Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia.
in Alzheimer's & dementia : the journal of the Alzheimer's Association
Mirza A
(2016)
The Identification of Aluminum in Human Brain Tissue Using Lumogallion and Fluorescence Microscopy.
in Journal of Alzheimer's disease : JAD
Mirza A
(2017)
Aluminium in brain tissue in familial Alzheimer's disease.
in Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
Murray CE
(2019)
APOE e4 is also required in TREM2 R47H variant carriers for Alzheimer's disease to develop.
in Neuropathology and applied neurobiology
Niblock M
(2016)
Lack of association between TDP-43 pathology and tau mis-splicing in Alzheimer's disease.
in Neurobiology of aging
Niblock M
(2016)
Retention of hexanucleotide repeat-containing intron in C9orf72 mRNA: implications for the pathogenesis of ALS/FTD.
in Acta neuropathologica communications
Nicolas A
(2018)
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.
in Neuron
Nolan M
(2015)
Control tissue in brain banking: the importance of thorough neuropathological assessment.
in Journal of neural transmission (Vienna, Austria : 1996)
Orme T
(2020)
Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.
in Acta neuropathologica communications
Paonessa F
(2019)
Microtubules Deform the Nuclear Membrane and Disrupt Nucleocytoplasmic Transport in Tau-Mediated Frontotemporal Dementia.
in Cell reports
Patel H
(2019)
Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains.
in Brain, behavior, and immunity
Perez-Nievas BG
(2021)
Astrocytic C-X-C motif chemokine ligand-1 mediates ß-amyloid-induced synaptotoxicity.
in Journal of neuroinflammation
Peters OM
(2015)
Gamma-synuclein pathology in amyotrophic lateral sclerosis.
in Annals of clinical and translational neurology
Pottier C
(2018)
Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.
in The Lancet. Neurology
Respondek G
(2017)
Which ante mortem clinical features predict progressive supranuclear palsy pathology?
in Movement disorders : official journal of the Movement Disorder Society
Respondek G
(2020)
Validation of the movement disorder society criteria for the diagnosis of 4-repeat tauopathies.
in Movement disorders : official journal of the Movement Disorder Society
Sala Frigerio C
(2015)
On the identification of low allele frequency mosaic mutations in the brains of Alzheimer's disease patients.
in Alzheimer's & dementia : the journal of the Alzheimer's Association
Sassi C
(2016)
Influence of Coding Variability in APP-Aß Metabolism Genes in Sporadic Alzheimer's Disease.
in PloS one
Sassi C
(2016)
ABCA7 p.G215S as potential protective factor for Alzheimer's disease.
in Neurobiology of aging
Sassi C
(2018)
Mendelian adult-onset leukodystrophy genes in Alzheimer's disease: critical influence of CSF1R and NOTCH3.
in Neurobiology of aging
Savage AL
(2020)
Frequency and methylation status of selected retrotransposition competent L1 loci in amyotrophic lateral sclerosis.
in Molecular brain
Selvackadunco S
(2019)
Comparison of clinical and neuropathological diagnoses of neurodegenerative diseases in two centres from the Brains for Dementia Research (BDR) cohort.
in Journal of neural transmission (Vienna, Austria : 1996)
Smethurst P
(2016)
In vitro prion-like behaviour of TDP-43 in ALS
in Neurobiology of Disease
Smith A
(2019)
Parallel profiling of DNA methylation and hydroxymethylation highlights neuropathology-associated epigenetic variation in Alzheimer's disease
in Clinical Epigenetics
Smith AR
(2019)
A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases.
in Neurobiology of aging
Smith AR
(2021)
The histone modification H3K4me3 is altered at the ANK1 locus in Alzheimer's disease brain.
in Future science OA
Smith BN
(2017)
Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis.
in Science translational medicine
Smith BN
(2015)
Novel mutations support a role for Profilin 1 in the pathogenesis of ALS.
in Neurobiology of aging
Smith BN
(2014)
Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS.
in Neuron
Smith RG
(2018)
Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology.
in Alzheimer's & dementia : the journal of the Alzheimer's Association
Solomon DA
(2018)
A feedback loop between dipeptide-repeat protein, TDP-43 and karyopherin-a mediates C9orf72-related neurodegeneration.
in Brain : a journal of neurology
Strobel S
(2015)
Changes in the expression of genes related to neuroinflammation over the course of sporadic Alzheimer's disease progression: CX3CL1, TREM2, and PPAR?.
in Journal of neural transmission (Vienna, Austria : 1996)
Tiwari SS
(2016)
Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss.
in Brain : a journal of neurology
Tiwari SS
(2015)
Evidence that the presynaptic vesicle protein CSPalpha is a key player in synaptic degeneration and protection in Alzheimer's disease.
in Molecular brain
Description | MRC London Neurodegenerative Diseases Brain Bank |
Amount | £1,229,499 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2013 |
End | 09/2018 |
Title | MRC brainbank tissue database |
Description | Database of all tissue held in the UK Brain bank network - searchable by registered users |
Type Of Material | Database/Collection of data |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Increased accessibility to tissue |
URL | https://www.mrc.ac.uk/research/facilities-and-resources-for-researchers/brain-banks/ |
Description | Brains for Dementia Research |
Organisation | Cardiff University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Projects are ongoing |
Collaborator Contribution | Collaborative research projects, sharing of tissueCollaborative Research projects and sharing of tissueCollaborative research projects and sharing of tissueCollaborative research projects and sharing of tissue |
Impact | Increased numbers of brain donors, who will have thourough clinical assesments prior to donation. |
Start Year | 2008 |
Description | Brains for Dementia Research |
Organisation | Newcastle University |
Department | Institute for Ageing and Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Projects are ongoing |
Collaborator Contribution | Collaborative research projects, sharing of tissueCollaborative Research projects and sharing of tissueCollaborative research projects and sharing of tissueCollaborative research projects and sharing of tissue |
Impact | Increased numbers of brain donors, who will have thourough clinical assesments prior to donation. |
Start Year | 2008 |
Description | Brains for Dementia Research |
Organisation | University of Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Projects are ongoing |
Collaborator Contribution | Collaborative research projects, sharing of tissueCollaborative Research projects and sharing of tissueCollaborative research projects and sharing of tissueCollaborative research projects and sharing of tissue |
Impact | Increased numbers of brain donors, who will have thourough clinical assesments prior to donation. |
Start Year | 2008 |
Description | Brains for Dementia Research |
Organisation | University of Manchester |
Department | Community-Based Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Projects are ongoing |
Collaborator Contribution | Collaborative research projects, sharing of tissueCollaborative Research projects and sharing of tissueCollaborative research projects and sharing of tissueCollaborative research projects and sharing of tissue |
Impact | Increased numbers of brain donors, who will have thourough clinical assesments prior to donation. |
Start Year | 2008 |
Description | Brains for Dementia Research |
Organisation | University of Oxford |
Department | Oxford Centre for Human Brain Activity (OHBA) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Projects are ongoing |
Collaborator Contribution | Collaborative research projects, sharing of tissueCollaborative Research projects and sharing of tissueCollaborative research projects and sharing of tissueCollaborative research projects and sharing of tissue |
Impact | Increased numbers of brain donors, who will have thourough clinical assesments prior to donation. |
Start Year | 2008 |
Description | Brains for Dementia Research 3 |
Organisation | Alzheimer’s Brain Bank UK |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Partner brain bank |
Collaborator Contribution | Supporting charity |
Impact | Joint publications |
Start Year | 2018 |
Description | MND research event talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | MND research event - Sussex area |
Year(s) Of Engagement Activity | 2019 |
Description | Pint of Science talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Team member gave a talk for the 'Pint of Science' series in a London pub to approx. 50 people |
Year(s) Of Engagement Activity | 2015 |
Description | Public Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Participants in your research and patient groups |
Results and Impact | increased awareness of research n/a |
Year(s) Of Engagement Activity | 2014 |
Description | Public awareness day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | lots of interesting questions asked n/a |
Year(s) Of Engagement Activity | 2014 |