A newly found molecule could light up the tau proteins long associated with neurodegenerative diseases, giving doctors a new tool to diagnose Alzheimer’s disease.
In a pair of studies a team from Johns Hopkins Medicine have found new radioactive trace molecules that bind to and light up tau tangles in the human brain, opening the door to both diagnose Alzheimer’s disease better and learn more about the tau proteins commonly associated with the disease.
“One of the greatest public health challenges is Alzheimer’s disease, for which there currently is no cure and no definitive diagnostic until autopsy,” Dean Wong, MD, PhD, professor of radiology and radiological sciences, psychiatry and behavioral sciences, neurology and neuroscience, and director of the Section of High Resolution Brain PET Imaging, Division of Nuclear Medicine at the Johns Hopkins University School of Medicine, said in a statement. “We have been working hard to identify new radiopharmaceuticals that can help speed the discoveries of diagnostics and treatments for these devastating neurodegenerative disorders.”
Alzheimer’s disease is characterized by the presence of two abnormal protein structures—amyloid plaques and tangled fibers comprised of tau proteins. However, gaining a better understanding of Alzheimer’s and other related dementias remains a challenge due to our lack of understanding as to how the neurofibrillary tangles develop in real time.
Previously, the researchers tested a collection of about 500 potential tracer molecules and narrowed down a handful of candidates Tau PET radiopharmaceuticals. They eventually settled on the three promising tracers that were previously tested in non-human primates.
To test the tracers in humans, the researchers recruited 12 Alzheimer’s patients, seven younger healthy controls between 25 and 38 years old, and five healthy controls older than 50 for brain-only PET scans. Six additional older healthy control volunteers received full-body scans.
For the first part of the three-part study, each volunteer was injected with two of the three randomly designated tracers. Then on a separate visit, they received a brain PET scan to determine which molecule performed best.
Next, the researchers tested the optimal tracer—F-18 RO948—with additional brain imaging in five patients with Alzheimer’s and five older controls. They also conducted a follow-up with previously seen patients to evaluate the potential progression of tau protein tangling after an average of about 16 months.
In the final component of the study, the researchers examined six older control volunteers who underwent whole-body scans.
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.
The researchers found that healthy brains retained little to no tracer, while the diseased brains showed tau in various regions of the brain like the temporal lobe, parietal lobe and occipital lobe.
In a second study, the researchers examined the detailed quantification of tau binding through F-18 RO948 in 11 patients with Alzheimer’s, five young cognitively normal control participants and five older cognitively normal control volunteers.
In this study they found that the new tracer does not bind randomly to other tissue like the currently used Tau tracer—F-18 AV1451.
The study was published in The Journal of Nuclear Medicine.