The role of epigenetics in Alzheimer’s disease, using mice as a model species
Ageing causes our cells to decline in both integrity and function. In healthy cells, our genes are tightly regulated so that the correct combination of genes are switched on, or off, at the proper time to allow for learning and memory to occur. This is achieved by the addition or removal of small chemical residues on top of the DNA, and the study of these processes is known as epigenetics. Epigenetic marks on our DNA can change during ageing, and diseases occur when this happens too quickly or in an uncontrolled way.
Proper epigenetic control must be maintained during ageing and Mr Phipps' PhD project raises the possibility that epigenetic dysregulation plays an important role in Alzheimer’s disease progression. The overall aim of his PhD is to identify epigenetic alterations associated with Alzheimer’s disease. Preliminary data has revealed that epigenetic changes do occur in people with Alzheimer’s disease. However, existing knowledge of the epigenetic alterations in Alzheimer’s disease is extremely limited, highlighting that new knowledge in this area is critical.
At completion of Mr Phipps' PhD he will understand whether distinct epigenetic signatures are associated with different stages of disease in Alzheimer’s disease, and if epigenetic changes occur in specific cell types in the brain or are dependent on proximity to AD pathology. These findings will significantly advance the understanding of the role of epigenetic dysregulation in Alzheimer’s disease and could also identify new clinical treatments for people with Alzheimer’s disease.
Phipps AJ, Vickers JC, Taberlay PC, Woodhouse A. (2016). Neurofilament-labelled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer’s disease. Neurobiology of Aging, 45, 30-42.
Vickers JC, Kirkcaldie MT, Phipps AJ, King AE (2016). Alterations in neurofilaments and the transformation of the cytoskeleton in axons may provide insight into the aberrant neuronal changes of Alzheimer's disease. Brain Research Bulletin, 126, 324-333.