Cerebral [18F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy

D. L. Dickstein; M. Y. Pullman; C. Fernandez; J. A. Short; L. Kostakoglu; K. Knesaurek; L. Soleimani; B. D. Jordan; W. A. Gordon; K. Dams-O'Connor; B. N. Delman; E. Wong; C. Y. Tang; S. T. DeKosky; J. R. Stone; R. C. Cantu; M. Sano; P. R. Hof; S. Gandy

doi:10.1038/tp.2016.175

Cerebral [¹⁸F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy

D. L. Dickstein, M. Y. Pullman, C. Fernandez, J. A. Short, L. Kostakoglu, K. Knesaurek, L. Soleimani, B. D. Jordan, W. A. Gordon, K. Dams-O'Connor, B. N. Delman, E. Wong, C. Y. Tang, S. T. DeKosky, J. R. Stone, R. C. Cantu, M. Sano, P. R. Hof, S. Gandy

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68 Scopus citations

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [¹⁸F] T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [¹⁸F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [¹⁸F]florbetapir was negative for amyloidosis. The [¹⁸F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [¹⁸F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr ≥ 1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [¹⁸F]T807/AV1451 retention requires postmortem correlation, our data suggest that [¹⁸F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTErelated tauopathy in living subjects.

Original language	English
Article number	e900
Journal	Translational Psychiatry
Volume	6
Issue number	9
DOIs	https://doi.org/10.1038/tp.2016.175
State	Published - 27 Sep 2016

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Dickstein, D. L., Pullman, M. Y., Fernandez, C., Short, J. A., Kostakoglu, L., Knesaurek, K., Soleimani, L., Jordan, B. D., Gordon, W. A., Dams-O'Connor, K., Delman, B. N., Wong, E., Tang, C. Y., DeKosky, S. T., Stone, J. R., Cantu, R. C., Sano, M., Hof, P. R., & Gandy, S. (2016). Cerebral [¹⁸F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy. Translational Psychiatry, 6(9), Article e900. https://doi.org/10.1038/tp.2016.175

@article{d4979ad0a5c147b1a8d5a693ab262e79,

title = "Cerebral [18F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy",

abstract = "Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F] T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr ≥ 1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTErelated tauopathy in living subjects.",

author = "Dickstein, {D. L.} and Pullman, {M. Y.} and C. Fernandez and Short, {J. A.} and L. Kostakoglu and K. Knesaurek and L. Soleimani and Jordan, {B. D.} and Gordon, {W. A.} and K. Dams-O'Connor and Delman, {B. N.} and E. Wong and Tang, {C. Y.} and DeKosky, {S. T.} and Stone, {J. R.} and Cantu, {R. C.} and M. Sano and Hof, {P. R.} and S. Gandy",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = sep,

day = "27",

doi = "10.1038/tp.2016.175",

language = "English",

volume = "6",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

number = "9",

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Dickstein, DL, Pullman, MY, Fernandez, C, Short, JA, Kostakoglu, L, Knesaurek, K, Soleimani, L, Jordan, BD, Gordon, WA, Dams-O'Connor, K , Delman, BN, Wong, E, Tang, CY, DeKosky, ST, Stone, JR, Cantu, RC, Sano, M , Hof, PR & Gandy, S 2016, 'Cerebral [¹⁸F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy', Translational Psychiatry, vol. 6, no. 9, e900. https://doi.org/10.1038/tp.2016.175

TY - JOUR

T1 - Cerebral [18F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy

AU - Dickstein, D. L.

AU - Pullman, M. Y.

AU - Fernandez, C.

AU - Short, J. A.

AU - Kostakoglu, L.

AU - Knesaurek, K.

AU - Soleimani, L.

AU - Jordan, B. D.

AU - Gordon, W. A.

AU - Dams-O'Connor, K.

AU - Delman, B. N.

AU - Wong, E.

AU - Tang, C. Y.

AU - DeKosky, S. T.

AU - Stone, J. R.

AU - Cantu, R. C.

AU - Sano, M.

AU - Hof, P. R.

AU - Gandy, S.

PY - 2016/9/27

Y1 - 2016/9/27

N2 - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F] T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr ≥ 1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTErelated tauopathy in living subjects.

AB - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F] T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr ≥ 1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTErelated tauopathy in living subjects.

UR - http://www.scopus.com/inward/record.url?scp=85007586839&partnerID=8YFLogxK

U2 - 10.1038/tp.2016.175

DO - 10.1038/tp.2016.175

M3 - Article

AN - SCOPUS:85007586839

SN - 2158-3188

VL - 6

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 9

M1 - e900

ER -

Cerebral [18F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy

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Cerebral [¹⁸F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy