Butyrycholinesterase activity and beta-amyloid plaques in mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive condition that causes cognitive and behavioural impairment. Currently, there is no means to diagnose the disease with certainty during life, and there is no cure. For confirmation of the disease the brain must be studied for the presence of plaques and tangles at autopsy. Plaques and tangles consist of improperly folded proteins and are believed to contribute to the progression of the disease. Butyrylcholinesterase (BuChE) is a protein that becomes associated with plaques and tangles in the AD brain and may play a role in their formation. This makes BuChE a suitable target for the development of new brain scanning methods for early diagnosis of AD during life, that could enable more timely treatment. To pursue this, we have developed a number of compounds that could be used to diagnose the disease by detecting abnormal BuChE activity through scans of the living brain. We have also developed other compounds that could be used to treat AD at an early stage to impede the disease process. A suitable animal model, one that resembles the conditions seen in the human disease, must first be used to test new drugs that target the BuChE that is associated with abnormal structures in AD. In preparation for such studies, the model must be fully understood. In the present study we will examine brain tissue from a mouse model that produces plaques having BuChE associated with them, as seen in post mortem analysis of human AD brain tissue. This should improve our understanding of the timing of the association between BuChE and plaque development. AD model mice of different ages of will be examined to determine when plaques form and when BuChE becomes associated with them. By understanding the association of BuChE with plaques in these experimental animals, we will be better able to test novel BuChE scanning methods to effect early diagnosis of AD during life and screen for drugs to prevent or slow progression of AD.