The Hope Center for Neurological Disorders and the Charles F. and Joanne Knight Alzheimer’s Disease Research Center (Knight ADRC) are working together on a joint initiative, Tau imaging in the course of Alzheimer’s disease.
Pathological hallmarks of Alzheimer disease include accumulations of neurofibrillary tangles as well as accumulations of extracellular amyloid beta (Aβ). The temporal pattern of Aβ accumulation is largely understood, thanks to the Pittsburgh B (PiB) imaging compound that binds Aβ, and can be seen using positron-emission tomography (PET) even years before symptom onset. A recently published study by Knight ADRC and Hope Center investigators took advantage of PiB imaging to show that Aβ deposition in the brain can be detected at least 15 years before symptom onset in persons destined to develop Alzheimer disease because they have a gene mutation that causes the disorder (Bateman et al., N Engl J Med 2012; 367:795-804).
In contrast to patterns of Aβ deposition, little is known about the accumulation of neurofibrillary tangles. This collaborative effort between the Hope Center and the Knight ADRC will test a marker generated by Avid Pharmaceuticals that is designed to label tau. By using this marker in a well-characterized cohort of volunteers recruited from the Knight ADRC, we hope to better understand how the timing of tau deposition compares to changes in the level of tau in cerebrospinal fluid (CSF), how it compares to other changes in the brain (e.g., hippocampal atrophy and cerebral hypometabolism), and how it relates to changes in Aβ in CSF and in brain.
The molecular imaging of neurofibrillary tangles is a new frontier for research in neurological disorders, and we look forward to sharing our progress.
Additional funding for this initiative is being provided by the BJHF/ICTS Clinical and Translational Service Research Award Program.
Brian A. Gordon, Karl Friedrichsen, Matthew Brier, Tyler Blazey, Yi Su, Jon Christensen, Patricia Aldea, Jonathan McConathy, David M. Holtzman, Nigel J. Cairns, John C. Morris, Anne M. Fagan, Beau M. Ances and Tammie L. S. Benzinger. The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging. Brain, 2016. doi:10.1093/brain/aww139
Matthew R. Brier, Brian Gordon, Karl Friedrichsen, John McCarthy, Ari Stern, Jon Christensen, Christopher Owen, Patricia Aldea, Yi Su, Jason Hassenstab, Nigel J. Cairns, David M. Holtzman, Anne M. Fagan, John C. Morris, Tammie L. S. Benzinger, Beau M. Ances. Tau and Ab imaging, CSF measures, and cognition in Alzheimer’s disease. Science Translational Medicine, 2016, 8(338).
Learn more about our partner in this initiative, the Knight Alzheimer's Disease Research Center.