"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 Alzheimers disease and other related dementias. Two studies will be published backtoback in the December issue of Journal of Nuclear Medicineone as featured article of the monthdescribing testing of three candidate molecules in patients with Alzheimers disease as well as the use of one molecule to measure the accumulation of tau proteins. One of the greatest public health challenges is Alzheimers disease for which there currently is no cure and no definitive diagnostic until autopsy says Dean Wong M.D. Ph.D. https 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. We have been working hard to identify new radiopharmaceuticals that can help speed the discoveries of diagnostics and treatments for these devastating neurodegenerative disorders. Alzheimers 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 Alzheimers disease thus far according to Wong is the inability to watch these socalled neurofibrillary tangles develop in real time. As part of a longer term project funded by F. HoffmanLa Roche the team previously tested a collection of approximately  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. The researchers recruited a total of  patients with Alzheimers disease seven younger healthy controls ages  years old and five older healthy controls age  or older for brainonly PET scans. An additional six older healthy controls were recruited for fullbody 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 subsequent evaluation to determine which molecule performed best. In the second part of the study researchers tested the optimal tracer called F RO with additional brain imaging in five patients with Alzheimers and five older controls with followup of previously seen patients to evaluate the potential progression of tau protein tangling after an average span of approximately  months.  The third part of the study examined six older controls undergoing wholebody scanning. In total the researchers looked at  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. Regions of the brain that typically contain accumulated tau protein include the temporal lobe parietal lobe and occipital lobe among others grey matter in the cerebellum is thought to contain low or no tau in patients with Alzheimers. They found that healthy brains retained little to no tracer whereas the brains of those with Alzheimers showed tau to be in regions of the brain consistent with previously reported postmortem data on filamentous tangles. In the second paper the team examined the detailed quantification of tau binding via F RO in  patients with Alzheimers disease five young cognitively normal controls and five older cognitively normal controls. They verified that detailed quantification of the tested and retested tracer in those five patients with Alzheimers and five older controls generated good and reproducible results. According to Wong this body of work reveals that as compared with the currently used Tau tracer F AV the new tracer F RO does not bind randomly to other tissue offering greater clarity into quantification of potential tau burden within the human brain. It really takes a village to make progress in biomedical research and this project was no exception with the involvement of the PET team at Hopkins a CRO who helped recruit healthy subjects colleagues in psychiatry and behavioral sciences colleagues at the National Institute of Aging and neuroscience imaging experts at Roche says Wong. This is a true example of crossdisciplinary collaboration and Im honored to have such great collaborators. This study was made available online in May  ahead of peerreview and publication. It was published in the December  issue of the journal.  Authors of the first Journal of Nuclear Medicine featured paper Characterization of  Novel Tau Radiopharmaceuticals CRO CRO and FRO in Healthy Controls and in Alzheimer Subjects httpjnm.snmjournals.orgcontent include Dean F. Wong Hiroto Kuwabara Paul B. Rosenberg Esther Oh  Constantine G. Lyketsos Noble George Lorena Gapasin Kelly Kitzmiller Josh Roberts Ayon Nandi James Brasic Chakradhar Mishra Abhay Moghekar Anil Mathur Marilyn Albert and Robert F. Dannals of The Johns Hopkins University Baltimore Maryland Robert A. Comley Susanne Ostrowitzki Cristina Vozzi Frank Boess Michael Honer Luca Gobbi Gregory Klein Jeff Sevigny and Edilio Borroni Pharma Research and Early Development HoffmannLa Roche Basel Switzerland and Susan M. Resnick and Madhav Thambisetty Lab of Behavior and Neuroscience NIHs National Institute on Aging Intramural Research Program Baltimore Maryland. This study was funded by an F. HoffmannLa Roche Ltd. contract to The Johns Hopkins University. Susan Resnick and Madhav Thambisetty are employees of the NIH National Institute on Aging. The authors report no other relevant potential conflict of interest."