In Vivo Studies

  • Tissue showing amyloid plaque burden
    Enhanced proteolysis of Aβ attenuates or completely prevents amyloidogenesis and downstream cytopathology in vivo.

    This figure shows severe amyloid plaque burden present in APP transgenic mice (center panel), which is markedly attenuated by approximately 100 percent overexpression of insulin-degrading enzyme (IDE; left panel) and completely prevented by approximately 700 percent overexpression of neprilysin (NEP; right panel).

    Source: Leissring MA, et al. Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology and premature death. Neuron. 2003;40:1087.

Enhanced proteolysis of Aβ attenuates or completely prevents amyloidogenesis and downstream cytopathology in vivo.

Mayo Clinic in Florida is internationally recognized for its excellence in developing novel murine models of neurodegenerative disease and has participated in the generation of some of the most widely used transgenic lines, including the Tg2576 model of Alzheimer's disease and the Tg4510 model of frontotemporal dementia.

The laboratory of Malcolm A. Leissring, Ph.D., uses these well-characterized animal models to test novel therapeutic approaches to treating and preventing neurodegenerative diseases. For example, Dr. Leissring's group was the first to show that neuronal overexpression of proteases that degrade the amyloid-beta (Aβ) protein can attenuate or even completely prevent Alzheimer-type pathology in amyloid precursor protein (APP) transgenic mice (see figure).

The discovery that proteolytic degradation of Aβ potently regulates amyloidogenesis has numerous implications for the pathogenesis and prevention of Alzheimer's disease. Dr. Leissring's laboratory is currently pursuing a number of very promising projects derived from this seminal discovery.