Work in this area has investigated disease mechanisms, the natural history and strategies for repair. Adult neurogenesis in the subventricular zone is regulated by dopamine through an epidermal growth factor regulated pathway and similar processes may also be important in the dentate gyrus of the hippocampus, the other site of constitutive neurogenesis in the mature central nervous system.
Adult hippocampal neurogenesis has been shown to have a specific role in memory involving pattern separation. This can now be studied clinically and modelled experimentally. The cognitive deficits in Parkinson's disease result either from frontostriatal damage to dopaminergic networks or posterior cortical involvement dependent upon Lewy body pathology; the former is determined by polymorphisms in genes that impact on dopaminergic function (COMT) whereas the latter is influenced by genes involved in the pathogenesis of Lewy body disease (Tau). These predictors of dementia allow better screening of patients for therapeutic trials. These include novel cell based treatments (TRANSEURO) and optimised delivery of more conventional treatments such as cholinesterase inhibitors (MUSTARDD study). A method has been developed for protecting dysfunctional and dying neurons in Parkinson's disease using a specific non-coding RNA from cytomegalovirus. Work in Huntington's disease has defined the extent of sleep and metabolic abnormalities and this will inform the selection of patients for clinical trials. Biomarkers based on metabanomics have been developed that distinguish patients with Parkinson's disease from progressive supranuclear palsy in which the dementia is attributed to loss of frontal grey matter leading to impairments of social and emotional cognition. Based on mapping the neural landscape of Alzheimer's disease, a novel neuropsychological test has been designed to discriminate Alzheimer's from semantic dementia using the comparative distribution of lesions and activation patterns in navigation memory demonstrated by fMRI. Computational methods have been used to develop image analysis from historical datasets, enabling the discrimination of typical fronto-temporal dementia from variants with Alzheimer pathology. As with all other disease related research, close contact is maintained with patients and their carers providing a support group that also offers a forum in which to discuss issues such as whether the introduction of disease-modifying therapy that prolongs but does not cure the disease prolonging is welcome (it is not). Much of the work on neurodegenerative disease is supported by platform funding for the Brain Bank.