Alzheimer's - Dementia, Author Interviews, Brain Injury, Medical Imaging, UCSF / 06.01.2020
Tau Pet Scanning In a Former NFL Play with CTE
MedicalResearch.com Interview with:
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Dr. Mantyh[/caption]
William G. Mantyh, MD
Clinical Fellow, UCSF Memory and Aging Center
Weill Institute for Neurosciences
UCSF
MedicalResearch.com: What is the background for this study?
Response: Similar to Alzheimer’s disease (AD) and other dementing illnesses, Chronic Traumatic Encephalopathy (CTE) is a progressive neurodegenerative condition associated with abnormally folded tau protein in the brain. CTE is thought to be caused by exposure to repetitive head trauma, and recently has been the subject of intense media coverage given the frequency of CTE found in brains of deceased former American professional football players. CTE is almost impossible to confidently diagnose during life as the symptoms are diverse and vary from patient-to-patient. Symptoms can include impairments in memory, multi-tasking, behavioral/mood regulation, and movement. As there are no blood, imaging, or other tests for this disease, one active area of research is developing a test to help doctors diagnose this condition.
As tau tangles in CTE are similar in many respects to those in Alzheimer’s disease, there was hope that PET tracers that detect tau in AD might also work in CTE. Flortaucipir (FTP) is probably the most widely used tau tracer in AD. Recent work has reported some signal from FTP-PET in symptomatic former NFL players and other patients at risk for CTE (Stern et al. New Engl Jour Med 2019; Lesman-Segev et al. Neuroimage Clinical 2019). The overall signal was lower than that observed in Alzheimer’s disease, and, in lieu of correlations with post-mortem findings, it was unclear how well FTP binds to tau pathology in CTE.
Dr. Mantyh[/caption]
William G. Mantyh, MD
Clinical Fellow, UCSF Memory and Aging Center
Weill Institute for Neurosciences
UCSF
MedicalResearch.com: What is the background for this study?
Response: Similar to Alzheimer’s disease (AD) and other dementing illnesses, Chronic Traumatic Encephalopathy (CTE) is a progressive neurodegenerative condition associated with abnormally folded tau protein in the brain. CTE is thought to be caused by exposure to repetitive head trauma, and recently has been the subject of intense media coverage given the frequency of CTE found in brains of deceased former American professional football players. CTE is almost impossible to confidently diagnose during life as the symptoms are diverse and vary from patient-to-patient. Symptoms can include impairments in memory, multi-tasking, behavioral/mood regulation, and movement. As there are no blood, imaging, or other tests for this disease, one active area of research is developing a test to help doctors diagnose this condition.
As tau tangles in CTE are similar in many respects to those in Alzheimer’s disease, there was hope that PET tracers that detect tau in AD might also work in CTE. Flortaucipir (FTP) is probably the most widely used tau tracer in AD. Recent work has reported some signal from FTP-PET in symptomatic former NFL players and other patients at risk for CTE (Stern et al. New Engl Jour Med 2019; Lesman-Segev et al. Neuroimage Clinical 2019). The overall signal was lower than that observed in Alzheimer’s disease, and, in lieu of correlations with post-mortem findings, it was unclear how well FTP binds to tau pathology in CTE.
Dr. Dunn[/caption]
Dr. Amy Dunn, PhD
Kaczorowski lab
The Jackson Laboratory
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Environmental factors, such as a poor diet, are known risk factors for Alzheimer’s disease. But the mechanisms are complex, and it is not known how such environmental perturbations interact with individual genetic variation to confer disease risk. Previous studies have not adequately addressed how the combination of genetic variant and environmental factors combine to alter cognitive response to a poor diet.
To investigate gene-by-environment interactions, we fed either a normal diet or a high-fat diet to a genetically diverse Alzheimer’s disease mouse model population starting at six months of age and monitored metabolic and cognitive function.
We observed accelerated working memory decline in the mice on the high-fat diet after eight weeks, with substantial gene-by diet effects on both cognitive and metabolic traits.
Metabolic dysfunction was more closely related to cognitive function in mice carrying Alzheimer’s mutations than in those without. Interestingly, the high-fat diet affected metabolic function differently in female versus male mice. 
Dr. Mikkola[/caption]
Tomi Mikkola MD
Associate Professor
Helsinki University Hospital
Department of Obstetrics and Gynecology
Helsinki, Finland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In Finland we have perhaps the most comprehensive and reliable medical registers in the world. Thus, with my research group I have conducted various large studies evaluating association of postmenopausal hormone therapy use and various major diseases (see e.g. the references in the B;MJ paper). There has been various smaller studies indicating that hormone therapy might be protective for all kinds of dementias, also Alzheimer’s disease.
However, we have quite recently shown that hormone therapy seems to lower the mortality risk of vascular dementia but not Alzheimer’s disease (Mikkola TS et al. J Clin Endocrinol Metab 2017;102:870-7). Now in this upcoming BMJ-paper we report in a very large case-control study (83 688 women with Alzheimer’s disease and same number of control women without the disease) that systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer’s disease.
Furthermore, this risk increase is particularly in women using hormone therapy long, for more than 10 years. This was somewhat surprising finding, but it underlines the fact that mechanisms behind Alzheimer’s disease are likely quite different than in vascular dementia, where the risk factors are similar as in cardiovascular disease. We have also shown how hormone therapy protects against cardiovascular disease, particularly in women who initiate hormone therapy soon after menopause.
