UKPDSTB General: Brain Bank Bulletin issue 8, page 3

Page 3 of 4 Brain Bank Bulletin
The PDS Tissue Bank is sponsored by the Parkinson's Disease Society Issue 8
Spring 2007

Inside this issue:

Questions 1 Research Report:
Dementia and Hallucinations 2 Research Report:
RNA Quality 3 Contact Info 4

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We designed a study selecting PD cases to isolate clinical features of interest and study the underlying anatomical and pathological basis. The medical histories of 81 cases from the UK Parkinson’s Disease Society Tissue Bank were retrospectively examined and a severity score for dementia and visual hallucinations attributed without prior knowledge of the neuropathological diagnosis. Subsequently, cases with neuropathologically and clinically confirmed PD were grouped on the basis of clinical phenotype representing the extremes of a spectrum for dementia and visual hallucinations. Hence, we investigated the type of pathology and areas in which it was present in the following groups:

Fig 3. The cingulate gyrus of a Parkinson's disease patient containing beta-amyloid.

without dementia and visual hallucinations (9 cases),
with severe visual hallucinations and no dementia (5 cases),
with severe dementia and no visual hallucinations (4 cases) and
with severe dementia and visual hallucinations (12 cases).

Immunostaining was used to assess the extent of alpha-synuclein, tau and beta-amyloid deposition in eight brain regions affected in PD and known to subserve cognitive function.

In our study we have found a clinical relevance of the abnormally deposited protein alpha-synuclein in the limbic system with respect to the occurrence of both dementia and hallucinations in PD. This system is a complex set of structures involved in emotions (e.g. fear, aggression), motivation, formation of memory and cognitive and attentional processing. In addition, it is highly interconnected with other brain structures that are also involved in cognitive functions (e.g. nucleus accumbens and prefrontal cortex). There is also evidence that the limbic system provides a custodial function for the maintenance of a healthy conscious state of mind.

An improved understanding of the anatomical and pathological basis of cognitive and psychiatric symptoms in PD may ultimately contribute towards the evolution of better treatment strategies for these aspects of the illness. By studying the relationship between centres in the brain that control behaviour in Parkinson’s disease state, one will by inference add to a greater understanding of brain function in normal individuals.
Mr Michail Kalaitzakis, PhD Student

Research Project Report: Parkinson’s disease post-mortem brain tissue for RNA quality analysis

Introduction:
Brain Net Europe II is a consortium of European tissue banks collecting human post-mortem brains for various research purposes. The aim of the consortium is to standardise experimental techniques by developing optimal protocols and spreading these across the network. This is important as it will allow researchers requiring tissue to obtain tissue from any of the Tissue Banks and be able to compare the research results. The UK Multiple Sclerosis and Parkinson's disease tissue banks at Imperial College London are members of this network providing human brain tissue for research.
Human post-mortem brain tissue is one of the most valuable resources available for research into human neurological disorders. The success of experiments and reliability of data obtained from a molecular analysis of the tissue will depend on the quality of genetic material (RNA) obtained from this post-mortem tissue. RNA will be analysed using different variables to see if any of the factors affect the quality of the RNA. This will give us information on how best to obtain and store tissue i.e. with time delays etc...
Experiment:
Post-mortem brain tissue provided by the PD tissue bank was used in a collaborative experiment by the network members to determine the factors that affect the quality of RNA in the human postmortem brain in order to determine its suitability for molecular biological analyses. The quality of RNA can be affected by biological and clinical factors, which include the;

cause of death;
post-mortem delay; and the
method and duration of storage of brain tissue before it is used for RNA isolation.

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