Unraveling Alzheimer's: Clues May Be Found Visualizing Plaques In Human Brain, Mad Cow-type Diseases

“This amyloid tracer IMPY—which detects amyloid plaques in the human brain—provides an excellent starting point for parallel research in humans and animals,” said Denis Guilloteau, a biophysics professor and radiopharmacist in the nuclear medicine department of the Centre Hospitalier Universitaire Tours (CHRU) in France. “With IMPY, we were able to visualize abnormal protein in both neurodegenerative diseases—Alzheimer’s and scrapie—and this could provide new directions for future research,” he added. There are similarities between the loss of brain function in prion diseases and in Alzheimer’s disease, and an understanding of prion diseases will add to the understanding of what happens to the brain with Alzheimer’s disease, explained the co-author of “IMPY, a Beta-Amyloid Imaging Probe for Prion Detection.” In addition, the tracer may be used for research in the veterinary field, he noted.

Alzheimer’s disease is a progressive, irreversible brain disorder with no known cause or cure. Symptoms may include memory loss, confusion, impaired judgment, disorientation and loss of language skills. More than 4.5 million Americans are believed to have Alzheimer’s disease, and by 2050, the number could increase to 13.2 million.

Prions are abnormal, transmissible agents—with no DNA—that are able to induce abnormal folding of normal cellular prion proteins in the brain, leading to brain damage and the characteristic signs and symptoms of the disease. Prions cause a number of rare progressive neurodegenerative disorders that affect both humans and animals, and the diseases are usually rapidly progressive and always fatal. Creutzfeldt-Jakob disease is a rare, degenerative human brain disorder. Scrapie is a degenerative disease that affects the nervous systems of sheep and goats, and it is related to mad cow disease. Currently, a brain autopsy is necessary to obtain a definite diagnosis for Alzheimer’s and Creutzfeldt-Jakob. Guilloteau noted that investigating the prion animal diseases could form a model for future research in human disease. “It is important to study human neurodegenerative diseases and animal prion diseases in parallel,” he said.

Developing molecular agents such as IMPY may be useful for diagnosis and monitoring the progression of Alzheimer’s, noted Guilloteau. “The beta-amyloid tracer—developed by University of Pennsylvania researchers—is a very promising tool that may be used to discern an early diagnosis of Alzheimer’s with single photon emission computed tomography (SPECT), an imaging method available in many hospitals,” he added.

In the study, researchers used radioiodinated IMPY to bind to prion deposits in infected mice brain sections. Autoradiography, a procedure where an image is produced on photographic film by the radiation from a radioactive substance, showed a good visualization of these prion deposits, said Guilloteau. Major accumulations of radioactivity were seen in the cortex, colliculus, hippocampus, thalamus, cerebellum and pons. “Additional work needs to focus on the progression of disease in our animal model in vivo, and we must correlate the images with clinical symptoms,” he added.