Project No.2255

Primary Supervisor

Prof Jessica Teeling – University of Southampton

Co-Supervisor(s)

Prof Paul Skipp – TopMD Precision Medicine Ltd

Dr Jay Amin – University of Southampton

Summary

People in England live longer than ever before, but not always in good health.

Many older people live with multiple long-term conditions, resulting in substantial risk of age-related disease and care needs. It is becoming increasingly evident that current diagnostic and prognostic tools are not sufficient to distinguish normal healthy ageing from age-related disease, including dementia. Thus, there is a clear need for an improved method to discriminate healthy ageing from those at risk of developing dementia. Many neurological diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease and Dementia with Lewy Bodies (DLB) present with overlapping cognitive, behavioural and/or movement symptoms, particularly in the early stages. Access to neuroimaging and fluid biomarkers have improved diagnosis, but these techniques fail to reliably identify the type of dementia or predict the rate of clinical disease onset or progression. These observations reflect the reality that the current guidelines and combinations of biomarkers to accurately distinguish health from disease are not perfect.

In this PhD studentship we will determine the value of immune signatures that can separate healthy ageing from dementia. We will apply cutting edge measurement of gene expression profiles of blood samples from healthy people and compare the gene profiles to individuals diagnosed with Alzheimer’s Disease, Parkinson’s Disease or Dementia with Lewy Bodies. Gene expression biomarkers will be identified using artificial intelligence-enhanced technology, developed at the University of Southampton. By applying mathematical topology, we will use biological pathways as coordinates for measuring the ‘shape’ of global gene expression, accurately representing the molecular phenotype as a robust ‘pathway biomarker’. This studentship will provide novel insight into biological pathways of the aging immune system that will help us to better understand healthy aging and how dysregulation can lead to increased risk of developing certain types of dementia.