UKPDSTB Researchers: Publications Arising from Existing Tissue Requests

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Introduction Requesting Tissue Procedure and forms Terms and conditions Existing Tissue Requests List of titles Reports Publications All details Case Database Queen Square Brain Bank	Previous page: Reports on Tissue Requests	Existing Requests	Next page: Tissue Request Details
	Publications The publications listed below may relate to multiple tissue requests. Click on the tissue request (TR) number for further details on a particular project, if available. TR2 TR3 TR11 TR15 TR16 TR17 TR19 TR22 TR23 TR25 TR29 TR30 TR32 TR33 TR35 TR36 TR37 TR38 TR44 TR2, 23 and 29 Eblan MJ, Walker JM, Sidransky E. The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2005 Feb 17;352(7):728-31 TR3, 11, 30, 32, 33, 36, 37, 38 and 44 Duke DC, Moran LB, Kalaitzakis ME, Deprez M, Dexter DT, Pearce RK, Graeber MB. Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson's disease. Neurogenetics. 2006 May 13 Moran LB, Croisier E, Duke DC, Kalaitzakis ME, Roncaroli F, Deprez M, Dexter DT, Pearce RK, Graeber MB. Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra. Acta Neuropathol (Berl). 2007 Mar;113(3):253-63. Duke DC, Moran LB, Pearce RK, Graeber MB. The medial and lateral substantia nigra in Parkinson's disease: mRNA profiles associated with higher brain tissue vulnerability. Neurogenetics. 2007 Apr;8(2):83-94. Moran LB, Duke DC, Deprez M, Dexter DT, Pearce RK, Graeber MB. Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's. disease. Neurogenetics. 2006 Mar;7(1):1-11.
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Introduction Requesting Tissue Procedure and forms Terms and conditions Existing Tissue Requests List of titles Reports Publications All details Case Database Queen Square Brain Bank	TR2 TR3 TR11 TR15 TR16 TR17 TR19 TR22 TR23 TR25 TR29 TR30 TR32 TR33 TR35 TR36 TR37 TR38 TR44 TR15, 17, 19, 22 and 35 Croisier E, Moran LB, Dexter DT, Pearce RK, Graeber MB. Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. J Neuroinflammation. 2005 Jun 3;2:14. BACKGROUND: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease. METHODS: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course. RESULTS: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD. CONCLUSION: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution. PMID: 15935098 [PubMed] TR16 and25 Croisier E, Mres DE, Deprez M, Goldring K, Dexter DT, Pearce RK, Graeber MB, Roncaroli F. Comparative study of commercially available anti-alpha-synuclein antibodies. Neuropathol Appl Neurobiol. 2006 Jun;32(3):351-6. Immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis for Parkinson's disease, Dementia with Lewy bodies and Multiple System Atrophy (http://www.ICDNS.org). Nevertheless, no standardised protocol has been proposed. We have reviewed 242 of the 270 studies published until June 2005 that mentioned immunohistochemistry for anti-alpha synuclein on human tissue and we found that only 75 (31%) used commercial antibodies. We also noted that protocols, particularly dilution and antigen unmasking, varied between studies, even when the same antibody was employed. In order to establish a standardised protocol for alpha-synuclein immunohistochemistry, which can be applied in diagnostic neuropathology we tested seven commercial monoclonal antibodies in brains of subjects with Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, multiple sclerosis with incidental Lewy bodies and aged-matched normal brain and determined for each antibody the best suited protocol for antigen unmasking. We evaluated the intensity of immunolabelling in Lewy bodies, neuropil threads, dendrites, pre-synaptic terminals, granular cytoplasmic positivity, peri-axonal positivity, glial inclusions and non-specific immunolabelling. Although our results showed that all the antibodies detected alpha-synuclein inclusions, differences were noted between antibodies, particularly with regard to the detection of glial inclusions. From our study, the best antibodies of the seven tested appeared to be those directed against amino acids 116-131 and 15-123 and we suggest them to be used in routine diagnostic practice for alpha-synucleinopathies. PMID: 16640654 [PubMed - indexed for MEDLINE]
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