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Correlation of in Vivo [18F]Flortaucipir with Postmortem Alzheimer Disease Tau Pathology

Smith, Ruben LU ; Wibom, Moa LU ; Pawlik, Daria LU ; Englund, Elisabet LU and Hansson, Oskar LU (2019) In JAMA Neurology 76(3). p.310-310
Abstract

Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Therefore, there is a need to investigate the associations of tau PET with postmortem tau pathology in AD. Objective: To study the association of regional in vivo retention of the tau PET ligand [18F]flortaucipir (previously known as AV1451) with the density of tau neuropathology in the corresponding... (More)

Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Therefore, there is a need to investigate the associations of tau PET with postmortem tau pathology in AD. Objective: To study the association of regional in vivo retention of the tau PET ligand [18F]flortaucipir (previously known as AV1451) with the density of tau neuropathology in the corresponding brain regions in a patient with AD. Design, Setting, and Participants: The patient was a man in his 40s with AD caused by a PSEN1 mutation. Between May 2015 and December 2016, he underwent 2 [18F]flortaucipir PET scans at Lund University Hospital, Lund, Sweden. Postmortem analysis was performed 12 months after the last PET scan. Tau pathology was assessed using phosphorylated tau (AT8) immunohistochemistry and Gallyas silver staining. In addition to the regional total tau pathology burden, the density of tau-positive neurites and intrasomal tau tangles were quantified using a stereology-based method. Further, β-amyloid-containing plaques were detected using 4G8 immunohistochemistry. Data were analyzed between January 2018 and August 2018. Main Outcomes and Measures: Regional standardized uptake value ratios of [18F]flortaucipir were compared with the amount of tau pathology in the corresponding brain areas. Results: In this patient, the clinical disease symptoms progressed rapidly in life, paralleled with an annual increase of tau PET retention of 20% to 40% in many cortical regions. Compared with postmortem immunohistochemistry, regional in vivo uptake of [18F]flortaucipir was correlated with the density of tau-positive neurites (AT8: rs = 0.87; P <.001; Gallyas: rs = 0.92; P <.001), intrasomal tau tangles (AT8: rs = 0.65; P =.01; Gallyas: rs = 0.84; P <.001), and total tau burden (AT8: rs = 0.84; P <.001; Gallyas: rs = 0.82; P <.001). No correlations between [18F]flortaucipir and β-amyloid pathology were found. Conclusions and Relevance: These results indicate that [18F]flortaucipir PET retention is a robust in vivo measure of the total AD tau burden.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JAMA Neurology
volume
76
issue
3
pages
310 - 310
publisher
American Medical Association
external identifiers
  • scopus:85057834978
ISSN
2168-6149
DOI
10.1001/jamaneurol.2018.3692
language
English
LU publication?
yes
id
64d0d000-127b-43fa-b571-0ab2322ed5ff
date added to LUP
2018-12-20 14:31:48
date last changed
2019-07-16 04:02:24
@article{64d0d000-127b-43fa-b571-0ab2322ed5ff,
  abstract     = {<p>Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Therefore, there is a need to investigate the associations of tau PET with postmortem tau pathology in AD. Objective: To study the association of regional in vivo retention of the tau PET ligand [<sup>18</sup>F]flortaucipir (previously known as AV1451) with the density of tau neuropathology in the corresponding brain regions in a patient with AD. Design, Setting, and Participants: The patient was a man in his 40s with AD caused by a PSEN1 mutation. Between May 2015 and December 2016, he underwent 2 [<sup>18</sup>F]flortaucipir PET scans at Lund University Hospital, Lund, Sweden. Postmortem analysis was performed 12 months after the last PET scan. Tau pathology was assessed using phosphorylated tau (AT8) immunohistochemistry and Gallyas silver staining. In addition to the regional total tau pathology burden, the density of tau-positive neurites and intrasomal tau tangles were quantified using a stereology-based method. Further, β-amyloid-containing plaques were detected using 4G8 immunohistochemistry. Data were analyzed between January 2018 and August 2018. Main Outcomes and Measures: Regional standardized uptake value ratios of [<sup>18</sup>F]flortaucipir were compared with the amount of tau pathology in the corresponding brain areas. Results: In this patient, the clinical disease symptoms progressed rapidly in life, paralleled with an annual increase of tau PET retention of 20% to 40% in many cortical regions. Compared with postmortem immunohistochemistry, regional in vivo uptake of [<sup>18</sup>F]flortaucipir was correlated with the density of tau-positive neurites (AT8: r<sub>s</sub> = 0.87; P &lt;.001; Gallyas: r<sub>s</sub> = 0.92; P &lt;.001), intrasomal tau tangles (AT8: r<sub>s</sub> = 0.65; P =.01; Gallyas: r<sub>s</sub> = 0.84; P &lt;.001), and total tau burden (AT8: r<sub>s</sub> = 0.84; P &lt;.001; Gallyas: r<sub>s</sub> = 0.82; P &lt;.001). No correlations between [<sup>18</sup>F]flortaucipir and β-amyloid pathology were found. Conclusions and Relevance: These results indicate that [<sup>18</sup>F]flortaucipir PET retention is a robust in vivo measure of the total AD tau burden.</p>},
  author       = {Smith, Ruben and Wibom, Moa and Pawlik, Daria and Englund, Elisabet and Hansson, Oskar},
  issn         = {2168-6149},
  language     = {eng},
  number       = {3},
  pages        = {310--310},
  publisher    = {American Medical Association},
  series       = {JAMA Neurology},
  title        = {Correlation of in Vivo [<sup>18</sup>F]Flortaucipir with Postmortem Alzheimer Disease Tau Pathology},
  url          = {http://dx.doi.org/10.1001/jamaneurol.2018.3692},
  volume       = {76},
  year         = {2019},
}