About the project
In this PhD project, we aim to explore the influence of co-pathology on disease progression and response to treatment. The results may lead to improved understanding of the biological mechanism underlying disease in the DLB-affected brain.
Dementia with Lewy bodies (DLB) is characterized by the neuropathological presence of alpha synuclein (α-Syn) aggregates known as Lewy bodies. Despite clear neuropathological features, this clinical syndrome has marked heterogeneity of motor and cognitive symptoms with highly variable disease progression. The biological basis for this clinical heterogeneity remains poorly understood.
Experimental mouse studies have provided evidence that pathological synuclein burden is faster and more widespread when extracellular amyloid deposits are present. Co-pathology of Aβ and α-syn also increases neuronal loss, and progressive cognitive decline and motor performance. Potential mechanisms that explain how co-pathology triggers this enhanced disease progression include neuroinflammation and mitochondrial dysfunction, but this has not yet been studied in detail.
This studentship will develop an experimental mouse model for DLB and characterize levels of pathology, inflammation and mitochondrial (dys)function in brain.
You will use histology and molecular and cellular methods as readout of pathological changes. Following characterization of the co-pathology model, you will evaluate the efficacy of anti-amyloid antibodies and/or alternative/combined therapeutic strategies. Areas of impact: This studentship will increase our basic understanding of the biological mechanisms underpinning brain dysfunction associated with Lewy Body Disease. Identifying how α-Syn and Aβ co-pathology influences disease onset/progression will provide insight underlying mechanisms and contribute to novel strategies to treat Lewy Body Dementia.
You will also be supervised by organisations other than the University of Southampton, including Dr Daniel Erskine from Newcastle University.