TDP-43 is the characteristic pathology of some types of motor neuron disease and frontal temporal dementia. However, recent studies have demonstrated TDP-43 is also found in Alzheimer's disease, where it follows a distinct topographic sequence of progression (Joseph et al, 2014; 2016). Using tissue from the Newcastle Brain Tissue Resource, we are currently investigating TDP-43 expression in other age-related neurodegenerative disorders.
To date, our results have demonstrated that TDP-43 pathology is more severe and prevalent in Alzheimer's disease and mixed Alzheimer's disease/dementia with Lewy bodies, when compared to both dementia with Lewy bodies and aged controls. In control cases, the severity and prevalence of TDP-43 increases with advancing age. However, there does not appear to a relationship between TDP-43 and Lewy body pathology. This suggests that TDP-43 expression is an age-associated phenomenon but may be further aggravated by Alzheimer-type pathology. These results were published in the journal Brain Pathology.
Future work will include relating TDP-43 pathology with the pathological hallmarks of Alzheimer's disease (amyloid-beta and hyperphosphorylated tau) and other markers of degenerative brain changes in vulnerable regions of the brain. This will allow greater understanding of whether TDP-43 is related with particular pathologies or develops independently.
This project is led by Dr Kirsty McAleese, working alongside Dr Lauren Walker and Daniel Erskine.
This research was funded by the National Institute for Health Research (NIHR), Newcastle Biomedical Research Centre for Ageing and Age-related diseases, based at Newcastle Upon Tyne Hospitals, National Health Service (NHS) Foundation Trust and Newcastle University, the Alzheimer's society, the NIHR Biomedical Reseach Unit and Yvonne Emily Mairy bequest.
Publication:
McAleese KE, Walker L, Erskine D, Thomas AJ, McKeith IG, Attems J (2016) TDP-43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing. Brain Pathology [Epub ahead of print]