Amyloid Hypothesis

Our most advanced model system for screening Alzheimer's therapeutics is the aged dog. Dogs show a complex cognitive repertoire that is ideally suited for examining high level cognitive function. More importantly, they show both age-related cognitive dysfunction, including memory deficits that occur earliest in chronological time, as well as amyloid pathology that is nearly identical to that seen in humans. The amyloid cascade hypothesis proposes that increases in beta-amyloid cause neuronal dysfunction and loss ultimately resulting in dementia. Consequently, amyloid therapeutics currently receive the most attention in drug development. The aged dog represents a natural model system that is ideal for this target.

Ab immunostaining (Part A)Ab immunostaining (Part B)Ab immunostaining (Part C)Ab immunostaining (Part D)Ab immunostaining (Part E)Ab immunostaining (Part F)

Click on the images above to see magnified versions.

Dogs also show brain changes on MRI that parallel changes in Alzheimer's disease including brain atrophy and reduced levels of NAA, a marker of neuronal dysfunction. We have the capability to obtain serial CSF samples in ml quantities from dogs. These services are ideal for assessing brain biomarkers longitudinally, assessing the effects of your therapeutic on amyloid levels, or determining CNS penetrance of your therapeutic. Dogs also show cholinergic dysfunction and changes in mitochondrial function. Given the similarity of the aging dog to Alzheimer's patients, dogs have been used to study several therapeutic classes for Alzheimer's disease. Overall, dogs provide an excellent model for assessing therapeutic effects in a longitudinal fashion using similar approaches as those used in human clinical trials.