Alzheimer pathogenesis and pathophysiology.

Alzheimer pathogenesis and pathophysiology in a zebrafish model-Alzheimer's disease (AD) is the most prevalent form of dementia, affecting more than 20 million people worldwide, and the number of affected Canadians will rise sharply in coming years as the population ages. Better understanding of its aetiology is crucial for development of effective treatment, but is hampered by lack of adequate model systems to elucidate the molecular mechanisms involved. We propose that zebrafish can provide a valuable model for studying the pathogenesis and pathophysiology of AD. Zebrafish are more closely related to humans than common invertebrate biomedical models such as yeast, worms or flies. Their small size and transparency greatly aids optical investigation of the nervous system. I will exploit this for long-term, non-invasive observation of changes in an AD-model nervous system created by expression of AD-related mutations in transgenic fish, to gain insight into the slow progression of Alzheimer's disease. Furthermore, I will identify and characterize any learning abilities of the AD zebrafish to gain insight into the progression and physiological basis of cognitive impairments. Such learning-impaired fish may provide the basis for a high-througput screen to identify compounds of potential therapeutic value in AD.