Alzheimer’s Disease, Tet-off APP Transgenic Mouse Model

Alzheimer's disease is thought to arise from the accumulation of a small peptide termed amyloid-beta that is normally found in healthy individuals, but is abnormally abundant in the brains of AD patients. The peptide aggregates into extracellular lesions or amyloid plaques that are found throughout the hippocampus and cortex of affected individuals. Both amyloid pathology and the cognitive decline associated with AD can be recreated in transgenic mouse models for the disease. Mice overexpressing the human amyloid precursor protein (APP) with mutations identified from families with inherited AD generate high levels of amyloid-beta and form amyloid plaques similar to those used found in the brains of patients with AD.

The mouse BIRN will examine a transgenic mouse model for AD in which the expression of APP can be controlled with antibiotic treatment. We anticipate that this controllable transgenic mouse model can be used with MRI and the other methods employed by collaborators in the mouse BIRN to study the long-term kinetics of amyloid lesions in the brain under conditions similar to those expected from future AD therapies.