David Westaway, Ph.D.
University of Toronto
Toronto, Ontario, Canada

2003 Zenith Fellows Award

Ever since German neuropsychiatrist Alois Alzheimer described the first case, scientists have noted that Alzheimer’s disease involves two characteristic pathologies—amyloid plaques and neurofibrillary tangles. Understanding how these hallmark lesions relate to one another is an active area of research. An important part of this effort focuses on developing an animal model that produces both pathologies. Although scientists have achieved solid success in engineering mice that produce human amyloid, tangles have proved more elusive. Initial efforts resulted in animals that produced human tau, the protein involved in forming tangles, but did not develop tau deposits in the same brain regions in which humans develop tangles.

David Westaway, PhD, and his team are among the research groups that have recently achieved greater success in engineering mice that produce tau in the same brain regions where tangles form. The group has also previously engineered a mouse that forms significant plaque deposits and develops memory deficits as it ages. In this project, the group will crossbreed the two types of mice to gain insight into the combined effects of plaques and tangles, including whether amyloid deposits trigger tau pathologies. This question is of key significance for the “amyloid hypothesis,” the theory that amyloid is the prime suspect in Alzheimer’s disease. Other avenues of inquiry will explore whether tau deposits contribute to mental decline and the effects of other genes on both tau and amyloid. Results may significantly increase understanding of fundamental Alzheimer pathology.