Alzheimer's Disease & Other Dementias
Our research on Alzheimer’s disease and other dementias combines genetic, molecular, cellular and whole animal investigations of mechanisms underlying the development of neurodegenerative disease. We are actively researching candidate proteins suspected of being involved in disease pathogenesis, such as tau, beta-amyloid, TDP-43, and alpha-synuclein. In addition, proteins indicated by genetic studies are opening up new avenues for research.
has been instrumental in finding new candidate genes involved in Alzheimer’s disease. Large genome–wide association studies identified PICALM and clusterin, amongst others, as the first novel and statistically robust candidates after APOE to emerge from an Alzheimer’s disease GWAS study. This group is currently using whole exome capture and next generation sequencing of samples drawn from the MRC London Brain Bank for Neurodegenerative Diseases to elucidate candidate pathways involved in Alzheimer’s disease.
is studying the roles of protein kinases on tau phosphorylation in Alzheimer’s disease and other related disorders, including progressive supranuclear palsy and frontotemporal dementias. These studies use human brain tissue and cell models to investigate specific molecular mechanisms that underlie dementia. Other work involves investigation of tau protein interactions and trafficking, together with axonal transport deficits as potential contributory factors in dementia.
has particular interests in examining the mechanisms by which beta-amyloid and tau mediate synaptic and neuronal toxicity in Alzheimer’s disease. This group also uses cell and animal models of Alzheimer’s disease to investigate neuron-glial interactions and associated neuroinflammatory responses, in addition to calcium dysregulation and aberrant protein degradation in disease.
is studying axonal transport, signal transduction and mitochondrial abnormalities in the nervous system since there is evidence that these processes are disrupted in Alzheimer’s disease. This group is also investigating mechanisms underlying the downstream effects of X11s and Fe65s, two families of proteins that bind to and affect the processing of amyloid precursor protein.
has a major interest in TDP-43-mediated neurodegeneration. This group has generated loss-of-function and gain-of-function mutations in the Drosophila homologue of TDP-43. These flies recapitulate many of the principal phenotypes of TDP-43 dysfunction and are being used to identify interacting partners and signalling pathways as a means to elucidate mechanisms underlying neurodegeneration.
has a focus on signalling pathways in relation to p25, the truncated activator of cyclin-dependent kinase-5, and the major synaptic kinase calcium-calmodulin kinase II. This group is also involved in related studies addressing deficits in synaptic signalling in the early stages of Alzheimer’s disease. Much of this work is underpinned by sensitive behavioural assays that analyse the impact of disease-associated abnormalities on learning and memory.
Also working on these diseases: