Researchers at Johns Hopkins Medicine have identified in live human brains new radioactive “tracer” molecules that bind to and “light up” tau tangles, a protein associated with a number of neurodegenerative diseases including Alzheimer’s disease and other related dementias

Two studies will be published back-to-back in the December issue of Journal of Nuclear Medicine—one as the featured article of the month—describing testing of three candidate molecules in patients with Alzheimer’s disease, as well as the use of one molecule to measure the accumulation of tau proteins.

"One of the greatest public health challenges is Alzheimer’s disease, for which there currently is no cure and no definitive diagnostic until autopsy. We have been working hard to identify new radiopharmaceuticals that can help speed the discoveries of diagnostics and treatments for these devastating neurodegenerative disorders," said Dean Wong, M.D., professor of radiology and radiological sciences, psychiatry and behavioral sciences, neurology and neuroscience.

Alzheimer’s disease is characterized in the brain by the appearance of two abnormal protein structures: amyloid plaques and tangled fibers made up of a protein called tau. One of the biggest challenges in studying Alzheimer’s disease thus far, according to Wong, is the inability to watch these so-called neurofibrillary tangles develop in real time.

As part of a longer-term project funded by F. Hoffman-La Roche, the team previously tested a collection of approximately 550 potential tracer molecules and identified six promising tracers, eventually narrowing them down to three to be made and tested as candidate Tau PET radiopharmaceuticals. These three most promising tracers were previously tested in nonhuman primates, and the results looked promising enough to test in people.

Cleaner and improved PET scan results seen in live patients

The researchers recruited a total of 12 patients with Alzheimer’s disease, seven younger healthy controls (ages 25–38 years old) and five older healthy controls (age 50 or older) for brain-only PET scans. An additional six older healthy controls were recruited for full-body scanning. The study was divided into three parts.

In the first part, each person was injected with two of the three randomly designated tracers (on separate visits) prior to receiving a brain PET scan with the subsequent evaluation to determine which molecule performed best.

In the second part of the study, researchers tested the optimal tracer, called F-18 RO948, with additional brain imaging in five patients with Alzheimer’s and five older controls, with follow-up of previously seen patients to evaluate the potential progression of tau protein tangling after an average span of approximately 16 months.

The third part of the study examined six older controls undergoing whole-body scanning. In total, the researchers looked at 80 different regions in the brain to evaluate how well the tracers were taken up by the brain, how well they penetrated through the tissue and how specifically they bound to the tau protein rather than just sticking indiscriminately to anything.