BRACE - Raising money for research into dementia

Research into dementia is carried out all over the world but we are lucky in the South West to have a large group of scientists, clinicians and psychologists working in the Bristol area on different aspects of dementia research.

BRACE has no particular strategic approach to the type and scope of projects it will consider for funding except that they should be of the highest scientific quality and address an area of research that would ultimately lead to improvements in diagnosis, treatment or quality of life for sufferers of dementing conditions.

Applications are invited from researchers in the region on a regular basis, as funds allow. Each research project is assessed for suitability by the Trustees Scientific Advisory Committee (SAC) chaired by Professor Brian Pickering. Each project is then sent out for peer review to experts in the field of research of the project. The SAC then makes its recommendations for funding to the Trustees who approve funding.

 

Some of the current project areas that we support are:

 

• The Neurotrophins - balance between life and death Dr David Dawbarn and Dr Shelley Allen are leading a group who are clarifying the molecular processes underlying Alzheimer's disease which is crucial for the development of novel therapeutics.
  
  Much of their BRACE-funded research centres on a small group of brain cells, called cholinergic cells, which are affected very early in Alzheimer's disease. Degeneration of these cells results in memory and attention problems, and in addition their research suggests that they may also be involved in the initiation of the disease process.
  
  These cholinergic cells are unusual in the brain because they require a protein called nerve growth factor (NGF) for their maintenance. NGF is present in two forms: proNGF and 'mature' NGF. These interact with other proteins called 'receptors' on the surface of cholinergic cells. Mature NGF keeps cholinergic cells alive; evidence suggests that proNGF may lead to cell death. There is an increase in proNGF in Alzheimer's disease brain. Their theory is that there is a harmful imbalance in proNGF/NGF levels causing early degeneration of the cholinergic cells, which also leads to the loss of other neurons to which they connect.
  
  They are working, not only to understand the basic underlying mechanisms involved, but also to 'redress the balance'. One of their ongoing projects is to produce a drug which will mimic mature NGF and produce a beneficial response in the cholinergic cells, hopefully overcoming the harmful effects of proNGF.

   

• Visual attention in Alzheimer's disease and mild cognitive impairment The evidence of robust and significant deficits in many aspects of visual attention-related processing in AD has lead Dr Andrea Tales to consider the possibility that tests of such function may be of use in the search for early markers of this disease. Currently, the clinical diagnosis of Alzheimer's disease (AD) involves neuropsychological tests to assess the integrity of higher order cerebral functions such as memory, cognition, visual perception, language and executive function. However, the onset of AD is insidious and such tests tend to lack the sensitivity and specificity necessary to correctly diagnose the very early stage of the disease. This together with similar shortcomings in relation to assessing disease progression and response to treatment has prompted the search for disease markers based on other aspects of brain processing.
  
  BRACE is funding further work by Andrea Tales and her colleague, Dr Gillian Porter to extend studies in basic visual attention-related processing and the time sequence of information processing which is altered in AD. Further work is planned to determine the use of this as an early disease marker.

   

• Neurifibrillary tangles and TGFß signalling in Alzheimer's disease Dr Katy Chalmers is working with Dr Patrick Kehoe and Professor Seth Love in the Dementia Research Group. Her work is addressing an important area of how functions of the genes that protect the brain are impaired in Alzheimer's disease by the abnormal binding of one particular protein, (Smad3) in abnormal neurons. The TGFß signalling pathway is involved in protecting the brain cells, reducing inflammation and providing a network of molecules which support the brain cells so that they can function. One of the key proteins in the pathway, pSmad3 is found to be sequestered in neurofibrillary tangles, thus potentially preventing it from carrying out its normal functions that would provide protection to brain cells. If this project can show exactly what is taking place, therapies that counteract the binding may be possible, with significant impact on the way Alzheimer's disease is treated. This is at the forefront of international research and the availability of the material from the South West Brain Bank means that Katy has access to the relevant resources to carry out this project.

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