MR advances Alzheimer’s

The combination of small-animal MRI and transgenic mouse models of Alzheimer’s disease has emerged as a powerful new research tool, according to a review written by Dr. Clifford R. Jack Jr. and others at the Mayo Clinic College of Medicine in Rochester, Minn., and at the University of Minnesota Medical School in Minneapolis.

By studying people with early-onset familial Alzheimer’s disease, researchers have identified mutations that cause it. To create transgenic mouse models of the disease, they inserted one or more of these mutations into mice.

Currently, the most widely used amyloid-specific experimental contrast agent is Pittsburgh Compound B, but several other contrast agents are being developed as well. Other researchers have used the relative abundance of iron in amyloid plaques as a natural contrast agent, and some have employed the Congo red fluorophore to label plaques. Still others have used magnetic resonance spectroscopy, a technique related to MRI.

In their own labs, the Minnesota reviewers oversaw small-animal MRI and magnetic resonance spectroscopy experiments. Using both techniques, they found that the neural pathology of the mice resembled Alzheimer’s disease in several respects.

In a pilot study, they treated the mouse models with antibodies against amyloid. They used passive immunization, in which antibodies are administered externally, as opposed to active immunization, in which an organism is induced to create its own antibodies. They found that amyloid decreased with antibody administration.

They concluded that MRI and magnetic resonance spectroscopy of transgenic mouse models are useful research tools. They expect that these magnetic resonance techniques will one day be used to monitor treatment of neurodegenerative disorders in human patients. (The Neuroscientist, February 2007, pp. 38-48.)