25 Mar Tau Protein A Key Driver Of Cognitive Decline in Alzheimer’s disease
Medical Research: What is the background for this study? What are the main findings?
Dr. Murray: Our study investigates two of the hallmark brain pathologies that underlie Alzheimer’s disease, abnormally accumulated tau and amyloid proteins. While both are integral to diagnosing Alzheimer’s disease postmortem, their exclusive relationship with cognitive decline has been debated. Using a large series from our brain bank we found that while an increase in abnormal accumulation of both proteins shares a close relationship with a decline in cognition, tau is the key driver of decline. This was important for us to understand as the second part of our study investigated amyloid brain scanning. We found that amyloid brain scanning closely represents amyloid deposits and not tau in postmortem brain tissue. One particular aspect we focused on is the cutoff for what would be a amyloid-positive brain scan that indicates Alzheimer’s disease. Our study supports that currently available cutoffs correspond to a level of amyloid accumulation that occurs before Alzheimer’s disease has too far advanced.
Medical Research: What should clinicians and patients take away from your report?
Dr. Murray: Given the relationship exists between cognitive decline and amyloid if tau is not considered, amyloid brain scanning can still be used to monitor Alzheimer’s disease in lieu of a marker for tau accumulation. This will be important as lifestyle risk factors are explored as Alzheimer’s disease modifiers and as tau therapeutics or combination therapeutics become more available. More importantly perhaps, evaluation of amyloid brain scanning cutoffs should be considered for clinical trials evaluating inclusion and exclusion of research participants. This study would not be possible without the patient’s and families who so selflessly donated their brain tissue.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Murray: The next exciting chapter in the field of Alzheimer’s disease is the possibility of tau brain scanning. More work needs to be done make this possibility a reality. The combination of tau and amyloid brain scanning would enable clinicians to improve diagnostic accuracy and enhance efforts toward early detection. The shift toward Tau therapeutics will be a necessary step toward managing and hopefully one day preventing the effects of Alzheimer’s disease on cognitive decline.
Co-authors of the study are, from Mayo Clinic in Jacksonville: Neill Graff-Radford, M.D., Amanda Liesinger, Ashley Cannon, Ph.D., Bhupendra Rawal, M.S., Owen Ross, Ph.D., and Dennis Dickson, M.D.; from Mayo Clinic in Rochester: Val Lowe, M.D., Scott Przybelski, Joseph Parisi, M.D., Ronald Petersen, M.D., Ph.D., Kejal Kantarci, M.D., David Knopman, M.D., and Clifford Jack, Jr., M.D.; and Ranjan Duara, M.D., from Mount Sinai Medical Center.
MedicalResearch.com Interview with: Melissa Murray, Ph.D (2015). Tau Protein A Key Driver Of Cognitive Decline in Alzheimer’s disease