Jason Hinman, MD, PhD

Development of a Novel Mouse Model of Mixed Vascular- and Alzheimer’s -Caused Dementia

The two leading causes of dementia are Alzheimer’s disease and white matter stroke. Clinical and autopsy studies suggest that 50 percent of dementia patients have features of both Alzheimer’s diseases and white matter stroke. Despite this clinical overlap, it is unknown how white matter stroke and Alzheimer’s disease synergize to worsen outcome in both illnesses. A central question to this clinically observed co-morbidity is whether white matter stroke accelerates the progression of Alzheimer’s disease.

Dr. Hinman’s lab previously used a mouse model of focal white matter stroke to demonstrate axonal reorganization in cortical neurons after stroke. The group is now developing a novel mouse model of mixed dementia by combining transgenic mice, with a genetic background that promoted moderately delayed accumulation of amyloid plaques, with their model of white matter stroke. This approach will allow the introduction of stroke prior to the significant accumulation of Alzheimer’s disease pathology and allowing determination of how the two disorders synergize.

Using this model, the group seeks to determine how co-morbid white matter stroke accelerates the progressive cognitive impairments caused by Alzheimer’s disease, and whether white matter stroke accelerates Alzheimer’s disease pathology. This novel and clinically relevant approach to the study of two common age-related disorders will help develop a necessary and new translational model for the study of mixed dementia, as well as determine the neurobiologic relationship between white matter stroke and Alzheimer’s disease.