Mice help unravel Alzheimer's
Mice expressing human genes linked with Alzheimer's disease can be used to help unravel how the disease develops and for preclinical testing of potential therapies. Background Alzheimer's disease (AD) is an illness marked by neurodegeneration in the brain, causing gradual intellectual deterioration and ultimate loss of control over all body functions. Devastating for the afflicted patients and their families, AD is also a growing problem for society. As the population ages, incidence of the disease increases. By the year 2030, the number of AD cases in Europe is expected to exceed 5 million. Caring for an AD patient costs over 12,000 euros yearly. There is no effective treatment, no direct diagnostic test. Little is known about how the disease develops. A major breakthrough has come from identification of gene variants that either cause certain hereditary forms of AD or constitute risk factors. By expressing these genes and their normal counterparts in relatively simple systems (cultured cells and mice), it is possible to start to unravel the causes of AD and to devise therapeutic strategies. These are the aims of the EU project "Transgenic mouse and rat models for Alzheimer's disease". Description, impact and results The project focuses primarily on normal and mutated proteins and on the genes that code for them. The teams are using a variety of methods to study the roles of these proteins and the interactions between them. A particularly effective approach is to create strains of mice whose brains either fail to express the normal mouse equivalent of an AD-associated gene or express one or more of the incriminated human genes (transgenic mice). This has yielded mice that develop AD-like symptoms (anxiety, aggression, learning defects, etc.) and signs of neurodegeneration. They constitute animal models of AD and are being used to test the effect of drugs and therapeutic strategies. The project is yielding vital information about the normal functions of certain proteins in the brain and about what goes wrong in the brains of people suffering from Alzheimer's disease. Several pharmaceutical and biotechnology companies have shown interest in the mice models as a pre-clinical testing system, and contracts have already been signed. Working partnerships The work involves two teams that produce and characterise transgenic mice (Centre for Human Genetics, Katholieke Universiteit Leuven, Belgium, and the Centre for Genome Research, Edinburgh, UK); a group of brain experts (Addenbrooke's Hospital, Cambridge, UK); a unit specialising in viral gene therapy (Hopital de la Salpetriere, Paris, France); and a neurogenetics team (Interuniversitair Instituut Antwerp, Belgium).