TREATMENT EFFECTS IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER'S DISEASE: A MAGNETIC RESONANCE SPECTROSCOPY STUDY AFTER PASSIVE IMMUNIZATION

摘要

Despite the enormous public health impact of Alzheimer's disease (AD), no disease-modifying treatment has yet been proven to be efficacious in humans. A rate-limiting step in the discovery of potential therapies for humans is the absence of efficient non-invasive methods of evaluating drugs in animal models of disease. Magnetic resonance spectroscopy (MRS) provides a non-invasive way to evaluate the animals at baseline, at the end of treatment, and serially to better understand treatment effects. In this study, MRS was assessed as potential outcome measure for detecting disease modification in a transgenic mouse model of AD. Passive immunization with two different antibodies, which have been previously shown to reduce plaque accumulation in transgenic AD mice, was used as intervention. Treatment effects were detected by MRS, and the most striking finding was attenuation of myo-inositol (mlns) increases in APP-PS1 mice with both treatments. Additionally, a dose-dependent effect was observed with one of the treatments for mlns. MRS appears to be a valid in vivo measure of anti-Ap therapeutic efficacy in pre-clinical studies. Because it is noninvasive, and can detect treatment effects, use of MRS-based endpoints could substantially accelerate drug discovery.