Since 1986, our lab has had a very simple philosophy: find the genes and mutations which cause neurological disease: take those genes and mutations into cells and into transgenic animals and make animal (transgenic mouse) models of them to better understand the disease processes and to use those models to test therapies. This simple philosophy underpins the current organization of the lab. However, for many diseases we have been interested in, particularly Alzheimer?s disease, all the genes involved in the simple forms of the disease have been identified (the amyloid gene and presenilin 1 and 2). For Parkinson?s disease some of the ?simple? genes have been identified (synuclein and parkin) but others remain, and for frontal temporal dementia, the tau gene has been identified but there are likely to be others. Increasingly for these diseases, and also for other diseases we are interested in, such as stroke, we will be searching for risk factor genes such as the apolipoprotein E gene in late onset Alzheimer?s disease. A major focus of work in the lab will be to develop and use strategies designed to find such risk factor genes.

Finally, we will be continuing to use this genetic information to help us build animal models of disease which will be useful, both for developing an understanding of the pathogeneses of the disease, and also for developing treatments for these devastating disorders.

In Alzheimer?s disease, our work and that of others, suggested that mutations which led to disease signposted a pathologic biochemical pathway which lead to disease pathogenesis. In AD this pathway seems to be the ?amyloid cascade?. We think it is likely that this type of relationship exists between the different gene products in other diseases and this belief informs the cell biology work we undertake. Thus, we will be continuing to work on Alzheimer?s disease cell biology, both the presenilins and APP, and with other pathogenic gene products as we and others identify them. This philosophy will also underpin our work on the cell biology of Parkinson?s disease and the other diseases we are interested in.

Selected Publications: