John Graham Sled, Ph.D.
Hospital for Sick Children
Toronto, Ontario, Canada

2007 Investigator-Initiated Research Grant

The protein fragment beta-amyloid is a key suspect in Alzheimer’s disease. However, beta-amyloid is a normally occurring protein also found in the brains of people without the disease. One possible explanation for why beta-amyloid does not always cause Alzheimer’s may be that problems with blood circulation in the brain must also exist for the disease to progress. Scientists have observed that excess beta-amyloid in brain reduces the ability of the blood vessels to regulate blood flow. This dysregulation deprives the brain of the sufficient oxygen and nutrients it needs to function properly.

John Graham Sled, Ph.D., and colleagues propose to examine whether blood flow dysregulation is necessary for the progression of Alzheimer’s disease. The research team will use experimental mice that have been engineered to develop Alzheimer-like pathology at an early age. After treating the mice with medications that temporarily restore normal blood flow regulation in the brain, the team will determine whether these drugs delay the onset of memory problems and hinder the development of beta-amyloid plaques. The team will monitor the mice using a magnetic resonance imaging (MRI) system that has been adapted to efficiently scan large numbers of animals.

Results from this study may shed new light on the potential role of vascular pathology in Alzheimer’s disease. The study may also lead to novel vascular treatments for the disease.