Small and colleagues conducted an interesting study that used 2-(1-(6-[2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP), a molecular imaging probe that binds unselectively to tau neurofibrillary tangles and amyloid-β plaques. FDDNP was, in fact, the first PET probe used successfully in Alzheimer's disease to show neurofibrillary tangles and Aβ depositions. Here, Small and colleagues used FDDNP to investigate whether or not tau deposits could be detected in five retired National Football League (NFL) players, compared to five controls matched for age, education, and body mass. The NFL players were all symptomatic with a history of mood or cognitive symptoms, and all had mild cognitive impairment (MCI). One NFL player and two controls received CT scans instead of MRI scans for registration to PET imaging due to claustrophobia (parenthetically, such differences in tracing between CT/PET and MRI/PET can be problematic). Regions of interest were traced on the co-registered MRI or CT scans for subcortical brain regions that included caudate, putamen,...  Read more

Small and colleagues conducted an interesting study that used 2-(1-(6-[2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP), a molecular imaging probe that binds unselectively to tau neurofibrillary tangles and amyloid-β plaques. FDDNP was, in fact, the first PET probe used successfully in Alzheimer's disease to show neurofibrillary tangles and Aβ depositions. Here, Small and colleagues used FDDNP to investigate whether or not tau deposits could be detected in five retired National Football League (NFL) players, compared to five controls matched for age, education, and body mass. The NFL players were all symptomatic with a history of mood or cognitive symptoms, and all had mild cognitive impairment (MCI). One NFL player and two controls received CT scans instead of MRI scans for registration to PET imaging due to claustrophobia (parenthetically, such differences in tracing between CT/PET and MRI/PET can be problematic). Regions of interest were traced on the co-registered MRI or CT scans for subcortical brain regions that included caudate, putamen, thalamus, subthalamus, midbrain, and cerebellar white matter, as well as cortical regions that included amygdala, frontal, parietal, posterior cingulate, and medial and lateral temporal lobe regions. Findings revealed higher FDDNP signals in the amygdala and subcortical regions in the NFL players compared with controls. The investigators note that caution is needed in interpreting the findings, given the small sample size and the uncorrected statistical comparisons. Nonetheless, they conclude that these findings "are consistent with fibrillary tau deposition patterns observed at autopsy in CTE cases." They also observed higher FDDNP binding in NFL players with more concussions, again suggesting to them a link to reported tau deposition patterns at autopsy in NFL players.

While the study is interesting, it is based on a very small sample, and it is not obvious that FDDNP binding in regions of the brain that show tau deposition at autopsy in NFL players necessarily implies tau deposition in this study. The title "PET Scanning of Brain Tau in Retired National Football League Players: Preliminary Findings" was very exciting, as there is great interest in developing a tau-specific ligand, particularly to investigate in-vivo tau in NFL players in whom tau deposition, and not neuritic plaques, has been observed at autopsy (see McKee et al., 2009). But to see that FDDNP was used, which is non-specific in terms of tau, was disappointing. Small and colleagues also note themselves that "FDDNP is not specific for tauopathies." To date, there is no good PET tau ligand, although recent work in humans by Chien and colleagues (Chien et al., 2012) at Siemens is likely the closest to being on the mark.

References:
Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807. J Alzheimers Dis. 2012 Dec 12. Abstract

McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 2009 Jul;68(7):709-35. Abstract

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