Queen Square Brain Bank

Directors: Professor T. Warner and Professor J. Holton

Overview

Proportion of neurological disorders represented in the Queen Square Brain Bank (QSBB) archive in 2004. The QSBB is a specialist movement disorder brain bank.

The Queen Square Brain Bank for Neurological Disorders (QSBB) holds a unique archive of brains donated by individuals with neurodegenerative disease and neurologically normal controls. It specialises in parkinsonian movement disorders, including Parkinson’s disease and multiple system atrophy and holds the national collection of brains donated by individuals with progressive supranuclear palsy (PSP). Recently the collection has been developed to include donated brains from prospectively studied people with familial dementias, in collaboration with the Dementia Research Group. The QSBB also banks brains donated by people with dystonia and Gilles de la Tourette syndrome.

The Brain Bank aims to provide the highest-possible quality of brain tissue for neuropathological studies and for scientific research both in the UK and worldwide. The large collection of tissue is backed up by good clinical documentation and all material is fully evaluated by the QSBB’s neuropathologists. Its procedures have ethical committee approval and tissue comes from registered prospective donors with the informed consent of next-of-kin. The QSBB’s records of prospective donors complies with the Data Protection Act. Visit our donor site to find out more information on the brain donor scheme.

The Brain Bank holds a large archive of brains, sufficient to support statistically valid case-control studies. Brain tissue is stored as formalin-fixed, wax embedded blocks and is frozen, either at –20 °C or at –80 °C (flash-frozen). Tissue can be provided as slide-mounted sections, or as small blocks for neurochemistry, proteomics and DNA and RNA analysis. Flash-frozen material has excellent histological preservation and is suitable for in situ hybridization and immunohistochemistry. Case-control studies are matched for post-mortem delay and agonal status and are supplied blind. Clinical data related to the tissue supplied are made available on an anonymised basis. The QSBB is supported by the Institute of Neurology, the Reta Lila Weston Institute of Neurological Studies and the PSP (Europe) Association

The Queen Square Brain Bank is an associate member of BrainNet Europe.

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Requests for Tissue

The Brain Bank aims to provide the highest-possible quality of brain tissue for neuropathological studies and for basic scientific research. Our procedures have ethical committee approval and we comply with the Data Protection Act. If you would like to request material from us, please visit the tissue request page for more information.

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Current research

Current research at the QSBB and Reta Lila Weston Institute includes studies on Parkinson's disease related to PARK gene mutations, including DJ-1 (PARK 7), PINK1 (PARK6) and LRRK2/dardarin (PARK 8). Alpha synuclein is studied in relation to sporadic Parkinson's disease. Much of this research is concentrated on the study of the expression of these genes in post-mortem brain and exploration of their possible functions. The large, well documented case collection of the QSBB has also permitted detailed clinicopathological studies of different movement disorders, such as multiple system atrophy, progressive supranuclear palsy and frontotemporal dementias. Examples of rare diseases in the collection have enabled us to perform detailed description and study of entities such as the familial British and familial Danish dementias and neurofilament inclusion body disease. DJ-1 immunohistochemistry demonstrated that, in human control brain, this protein is largely astrocytic and not generally present in neurons, although in situ hybridization studies show that a number of human neuronal populations express low levels of DJ-1 mRNA in both control and Parkinson's disease brain. DJ-1 has not been shown to be present in pathological inclusions in Parkinson's disease, ie Lewy bodies (LB). However, it is closely associated with abnormally phosphorylated tau protein in neurofibrillary tangles in PSP and Alzheimer's disease, as demonstrated by immunohistochemical and confocal microscopy studies. In glia DJ-1 forms abnormal deposits in multiple system atrophy (glial inclusions) and in coiled bodies in PSP. In human brain there appears to be an alteration of DJ-1 function in these neurodegenerative conditions so that the protein is expressed more strongly in some neuronal populations than is the case in control brain. Cell culture studies are planned to explore the possible functions of DJ-1.

In a collaborative study carried out by several groups of the Department of Molecular Neuroscience we characterized the expression of PINK1 protein in normal human and sporadic Parkinson's disease brains in addition to Parkinson's cases with heterozygous PINK1 mutations. With brain fractionation studies we confirmed that PINK1 is localized to the mitochondrial membranes. In addition, we showed that PINK1 is present in a proportion of Lewy bodies in cases of sporadic Parkinson's disease and Parkinson's disease associated with heterozygous mutations in the PINK1 gene. Our studies provided for the first time in vivo morphological and biochemical evidence to support a mitochondrial localization of PINK1 and support the significance of mitochondrial dysfunction in the pathogenesis of Parkinson's disease.

Investigation of the distribution pattern of synphilin-1, an alpha-synuclein protein interactor and parkin (PARK2) in post-mortem human brain showed an overlapping pattern. Both proteins were present in LBs in both brain stem and cortex and in a number of neuronal populations throughout the brain. The colocalisation of synphilin-1 and parkin as seen in human neuronal inclusions, was also demonstrated in cell culture systems when challenged with proteasomal inhibitor MG132. This study confirmed the presence of synphilin-1 and parkin in majority of LBs and indicated an important role of synphilin-1 in neurodegeneration in PD.

The PARK8 protein, LRRK2 has also been studied in the QSBB cohort of PD brains and were shown to be present in a small percentage of brain stem LBs and was widely distributed in neurones in several brain regions; brain stem, midbrain, cerebellum and cortex and was seen in neuronal cytoplasm and processes. Further work is in progress to establish the LRRK2 substrates from human brain using biochemical approaches and to study mRNA expression.

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Page last modified on 15 oct 14 12:19