APRIL 2003

MR lights up Alzheimer's amyloid brain plaques

By: Catherine Carrington

CONTEXT: Researchers at the Mayo Clinic in Rochester, MN, have developed a gadolinium-labeled molecular probe that enables MR detection of amyloid brain plaques. These plaques, which both characterize Alzheimer's disease and are central to its pathology, are too small to be directly visualized with other imaging methods. Rather, physicians must rely on nonspecific and indirect measures such as changes in the volume of the hippocampus to make a preliminary evaluation, while awaiting a definitive diagnosis at autopsy. Although it is still in a preclinical stage, the new research has the potential to speed the diagnosis of Alzheimer's disease and, perhaps more important, to assist in the development of drugs for preventing and reversing the buildup of amyloid plaques.

RESULTS: The molecular probe, developed by Joseph F. Poduslo, Ph.D., and colleagues, consists of an amyloid-ß peptide with a selective affinity for Alzheimer's plaques. The Rochester group first modified the probe to enhance its ability to cross the blood-brain barrier, then labeled it with gadolinium-DTPA to enable contrast-enhanced MR imaging (Neurobiol Dis 2002;11:315-329).

The researchers injected the molecular probe into two types of live mice: a transgenic strain bred to develop amyloid plaques and another set with normal brains. The mice were sacrificed four hours after injection. Investigators removed each brain, embedded it in agar in a glass tube, and inserted the tube into a 10-mm radio-frequency coil. Using a 7T MR spectrometer with a mouse-sized 89-mm vertical bore, they performed T2- and T1-weighted imaging at very high resolution, acquiring 62.5 mm3 voxels.

After MR imaging, the researchers sectioned and stained the brains for pathological examination. In the transgenic mice, they found a strong correlation between plaques identified on histology and focal areas of accelerated T2 and T1 relaxation (visible as dark and bright spots, respectively). T2-weighted imaging proved to be nonspecific, however, depicting focal areas of accelerated relaxation in the brains of normal mice, despite the absence of histologic evidence of plaque. T1-weighted imaging fared better, demonstrating homogeneous signal intensity in normal brains.

IMPLICATIONS: The next step is to replicate the study's findings in live mice. Among the many challenges is substantially shortening the scan times, which stretched to more than 14 hours during the imaging of brain specimens. Poduslo said his team is using higher field strengths and specialized surface coils to accomplish this. Imaging in humans is still years away, he said.