FDDNP-PET Tau Brain Protein Binding Patterns in Military Personnel with Suspected Chronic Traumatic Encephalopathy¹

Article type: Research Article

Authors: Chen, Stephen T.^{a; 2} | Siddarth, Prabha^{a; b; 2} | Merrill, David A.^{a; b} | Martinez, Jacqueline^{a; b} | Emerson, Natacha D.^{a; b} | Liu, Jie^c | Wong, Koon-Pong^c | Satyamurthy, Nagichettiar^c | Giza, Christopher C.^d | Huang, Sung-Cheng^c | Fitzsimmons, Robert P.^e | Bailes, Julian^f | Omalu, Bennet^g | Barrio, Jorge R.^c | Small, Gary W.^{a; b; *}

Affiliations: [a] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA | [b] UCLA Longevity Center at the Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA | [c] Department of Medical and Molecular Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA | [d] Department of Neurosurgery at the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA | [e] Fitzsimmons Law Offices, Wheeling, WV, USA | [f] Department of Neurosurgery, North Shore University Health System and University of Chicago Pritzker School of Medicine, Evanston, IL, USA | [g] Department of Medical Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Sacramento, CA, USA

Correspondence: [*] Correspondence to: Gary W. Small, MD, Semel Institute, 760 Westwood Plaza, Los Angeles, CA 90024, USA. E-mail: gsmall@mednet.ucla.edu.

Note: [1] Presented in part at the International Psychogeriatrics Association Annual Meeting in September, 2016 in San Francisco, CA.

Note: [2] These authors contributed equally to this work.

Abstract: Background:Our group has shown that in vivo tau brain binding patterns from FDDNP-PET scans in retired professional football players with suspected chronic traumatic encephalopathy differ from those of tau and amyloid aggregate binding observed in Alzheimer’s disease (AD) patients and cognitively-intact controls. Objective:To compare these findings with those from military personnel with histories of mild traumatic brain injury(mTBI). Methods:FDDNP-PET brain scans were compared among 7 military personnel and 15 retired players with mTBI histories and cognitive and/or mood symptoms, 24 AD patients, and 28 cognitively-intact controls. Nonparametric ANCOVAs with Tukey-Kramer adjusted post-hoc comparisons were used to test for significant differences in regional FDDNP binding among subject groups. Results:FDDNP brain binding was higher in military personnel compared to controls in the amygdala, midbrain, thalamus, pons, frontal and anterior and posterior cingulate regions (p < 0.01–0.0001). Binding patterns in the military personnel were similar to those of the players except for the amygdala and striatum (binding higher in players; p = 0.02–0.003). Compared with the AD group, the military personnel showed higher binding in the midbrain (p = 0.0008) and pons (p = 0.002) and lower binding in the medial temporal, lateral temporal, and parietal regions (all p = 0.02). Conclusion:This first study of in vivo tau and amyloid brain signals in military personnel with histories of mTBI shows binding patterns similar to those of retired football players and distinct from the binding patterns in AD and normal aging, suggesting the potential value of FDDNP-PET for early detection and treatment monitoring in varied at-risk populations.

Keywords: Alzheimer’s disease, brain tau and amyloid, chronic traumatic encephalopathy, FDDNP-PET, mild traumatic brain injury, military personnel, retired professional football players

DOI: 10.3233/JAD-171152

Journal: Journal of Alzheimer's Disease, vol. 65, no. 1, pp. 79-88, 2018