Detection of tau in Gerstmann-Sträussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET

Shannon L. Risacher, Martin Farlow, Daniel R. Bateman, Francine Epperson, Eileen F. Tallman, Rose Richardson, Jill R. Murrell, Frederick Unverzagt, Liana G. Apostolova, Jose Bonnin, Bernardino Ghetti, Andrew Saykin

Research output: Contribution to journalArticle

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Abstract

This study aimed to determine the pattern of [18F]flortaucipir uptake in individuals affected by Gerstmann-Sträussler-Scheinker disease (GSS) associated with the PRNP F198S mutation. The aims were to: 1) determine the pattern of [18F]flortaucipir uptake in two GSS patients; 2) compare tau distribution by [18F]flortaucipir PET imaging among three groups: two GSS patients, two early onset Alzheimer's disease patients (EOAD), two cognitively normal older adults (CN); 3) validate the PET imaging by comparing the pattern of [18F]flortaucipir uptake, in vivo, with that of tau neuropathology, post-mortem. Scans were processed to generate standardized uptake value ratio (SUVR) images. Regional [18F]flortaucipir SUVR was extracted and compared between GSS patients, EOADs, and CNs. Neuropathology and tau immunohistochemistry were carried out post-mortem on a GSS patient who died 9 months after the [18F]flortaucipir scan. The GSS patients were at different stages of disease progression. Patient A was mildly to moderately affected, suffering from cognitive, psychiatric, and ataxia symptoms. Patient B was moderately to severely affected, suffering from ataxia and parkinsonism accompanied by psychiatric and cognitive symptoms. The [18F]flortaucipir scans showed uptake in frontal, cingulate, and insular cortices, as well as in the striatum and thalamus. Uptake was greater in Patient B than in Patient A. Both GSS patients showed greater uptake in the striatum and thalamus than the EOADs and greater uptake in all evaluated regions than the CNs. Thioflavin S fluorescence and immunohistochemistry revealed that the anatomical distribution of tau pathology is consistent with that of [18F]flortaucipir uptake. In GSS patients, the neuroanatomical localization of pathologic tau, as detected by [18F]flortaucipir, suggests correlation with the psychiatric, motor, and cognitive symptoms. The topography of uptake in PRNP F198S GSS is strikingly different from that seen in AD. Further studies of the sensitivity, specificity, and anatomical patterns of tau PET in diseases with tau pathology are warranted.

Original languageEnglish (US)
Number of pages1
JournalActa neuropathologica communications
Volume6
Issue number1
DOIs
StatePublished - Oct 29 2018

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Psychiatry
Neurobehavioral Manifestations
Ataxia
Thalamus
Immunohistochemistry
Pathology
Gyrus Cinguli
Parkinsonian Disorders
Frontal Lobe
Cerebral Cortex
Disease Progression
Alzheimer Disease
Fluorescence
Sensitivity and Specificity
Mutation
Neuropathology
thioflavin T

Keywords

  • Gerstmann-Sträussler-Scheinker disease (GSS)
  • Positron emission tomography (PET)
  • Prion protein (PrP)
  • PRNP F198S mutation
  • Tau
  • [18F]flortaucipir/AV-1451/T-807

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Detection of tau in Gerstmann-Sträussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET. / Risacher, Shannon L.; Farlow, Martin; Bateman, Daniel R.; Epperson, Francine; Tallman, Eileen F.; Richardson, Rose; Murrell, Jill R.; Unverzagt, Frederick; Apostolova, Liana G.; Bonnin, Jose; Ghetti, Bernardino; Saykin, Andrew.

In: Acta neuropathologica communications, Vol. 6, No. 1, 29.10.2018.

Research output: Contribution to journalArticle

Risacher, Shannon L. ; Farlow, Martin ; Bateman, Daniel R. ; Epperson, Francine ; Tallman, Eileen F. ; Richardson, Rose ; Murrell, Jill R. ; Unverzagt, Frederick ; Apostolova, Liana G. ; Bonnin, Jose ; Ghetti, Bernardino ; Saykin, Andrew. / Detection of tau in Gerstmann-Sträussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET. In: Acta neuropathologica communications. 2018 ; Vol. 6, No. 1.
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AU - Farlow, Martin

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AU - Epperson, Francine

AU - Tallman, Eileen F.

AU - Richardson, Rose

AU - Murrell, Jill R.

AU - Unverzagt, Frederick

AU - Apostolova, Liana G.

AU - Bonnin, Jose

AU - Ghetti, Bernardino

AU - Saykin, Andrew

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N2 - This study aimed to determine the pattern of [18F]flortaucipir uptake in individuals affected by Gerstmann-Sträussler-Scheinker disease (GSS) associated with the PRNP F198S mutation. The aims were to: 1) determine the pattern of [18F]flortaucipir uptake in two GSS patients; 2) compare tau distribution by [18F]flortaucipir PET imaging among three groups: two GSS patients, two early onset Alzheimer's disease patients (EOAD), two cognitively normal older adults (CN); 3) validate the PET imaging by comparing the pattern of [18F]flortaucipir uptake, in vivo, with that of tau neuropathology, post-mortem. Scans were processed to generate standardized uptake value ratio (SUVR) images. Regional [18F]flortaucipir SUVR was extracted and compared between GSS patients, EOADs, and CNs. Neuropathology and tau immunohistochemistry were carried out post-mortem on a GSS patient who died 9 months after the [18F]flortaucipir scan. The GSS patients were at different stages of disease progression. Patient A was mildly to moderately affected, suffering from cognitive, psychiatric, and ataxia symptoms. Patient B was moderately to severely affected, suffering from ataxia and parkinsonism accompanied by psychiatric and cognitive symptoms. The [18F]flortaucipir scans showed uptake in frontal, cingulate, and insular cortices, as well as in the striatum and thalamus. Uptake was greater in Patient B than in Patient A. Both GSS patients showed greater uptake in the striatum and thalamus than the EOADs and greater uptake in all evaluated regions than the CNs. Thioflavin S fluorescence and immunohistochemistry revealed that the anatomical distribution of tau pathology is consistent with that of [18F]flortaucipir uptake. In GSS patients, the neuroanatomical localization of pathologic tau, as detected by [18F]flortaucipir, suggests correlation with the psychiatric, motor, and cognitive symptoms. The topography of uptake in PRNP F198S GSS is strikingly different from that seen in AD. Further studies of the sensitivity, specificity, and anatomical patterns of tau PET in diseases with tau pathology are warranted.

AB - This study aimed to determine the pattern of [18F]flortaucipir uptake in individuals affected by Gerstmann-Sträussler-Scheinker disease (GSS) associated with the PRNP F198S mutation. The aims were to: 1) determine the pattern of [18F]flortaucipir uptake in two GSS patients; 2) compare tau distribution by [18F]flortaucipir PET imaging among three groups: two GSS patients, two early onset Alzheimer's disease patients (EOAD), two cognitively normal older adults (CN); 3) validate the PET imaging by comparing the pattern of [18F]flortaucipir uptake, in vivo, with that of tau neuropathology, post-mortem. Scans were processed to generate standardized uptake value ratio (SUVR) images. Regional [18F]flortaucipir SUVR was extracted and compared between GSS patients, EOADs, and CNs. Neuropathology and tau immunohistochemistry were carried out post-mortem on a GSS patient who died 9 months after the [18F]flortaucipir scan. The GSS patients were at different stages of disease progression. Patient A was mildly to moderately affected, suffering from cognitive, psychiatric, and ataxia symptoms. Patient B was moderately to severely affected, suffering from ataxia and parkinsonism accompanied by psychiatric and cognitive symptoms. The [18F]flortaucipir scans showed uptake in frontal, cingulate, and insular cortices, as well as in the striatum and thalamus. Uptake was greater in Patient B than in Patient A. Both GSS patients showed greater uptake in the striatum and thalamus than the EOADs and greater uptake in all evaluated regions than the CNs. Thioflavin S fluorescence and immunohistochemistry revealed that the anatomical distribution of tau pathology is consistent with that of [18F]flortaucipir uptake. In GSS patients, the neuroanatomical localization of pathologic tau, as detected by [18F]flortaucipir, suggests correlation with the psychiatric, motor, and cognitive symptoms. The topography of uptake in PRNP F198S GSS is strikingly different from that seen in AD. Further studies of the sensitivity, specificity, and anatomical patterns of tau PET in diseases with tau pathology are warranted.

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