The SITraN neuropathology group is studying the pathology of brain ageing and its relationship to the development of dementia. The pathology of Alzheimer’s disease is characterised by neuro-fibrillary tangles and plaques, which can be identified in the brain using microscopy techniques and which are made of up two major proteins, ß-amyloid and tau.
Using donated brain tissue from a large population-based sample, the team has demonstrated that there is an overlap in the amounts of these two pathologies between people with and without dementia, particularly in the very oldest.
The group is therefore seeking to identify other cellular and molecular processes that also contribute to dementia aiming to refine understanding of the pathological basis of dementia and to identify potential new therapeutic targets.
The group has already discovered pathways that could serve as potential therapeutic targets. They have found defects in the insulin signalling pathway in human astrocytes, the cells surrounding neurons, and are now further investigating the role of astrocytes and defects in signalling pathways in the development of Alzheimer’s disease.
Further research addresses other risk factors involved in Alzheimer’s disease such as oxidative damage and vascular processes such as variations in blood flow to the brain, using novel imaging techniques in collaboration with Dr Jason Berwick from the University of Sheffield’s Department of Psychology.
CFAS is a population-based study established in 1993 that allows an examination of the spectrum of pathology that is present within a representative sample of more than 18,000 people aged over 65 years with the aim of investigating dementia and cognitive decline.
Sheffield is the lead centre for the neuropathology studies within CFAS and host of the Sheffield Brain and Tissue Bank (SBTB) which currently holds > 550 donated brains.
The study has been at the forefront of developing a new epidemiological approach to
brain pathology in dementia.