Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration

Alma Ghirelli; Nirubol Tosakulwong; Stephen D. Weigand; Heather M. Clark; Farwa Ali; Hugo Botha; Joseph R. Duffy; Rene L. Utianski; Marina Buciuc; Melissa E. Murray; Sydney A. Labuzan; Anthony J. Spychalla; Nha Trang Thu Pham; Christopher G. Schwarz; Matthew L. Senjem; Mary M. Machulda; Matthew Baker; Rosa Rademakers; Massimo Filippi; Clifford R. Jack; Val J. Lowe; Joseph E. Parisi; Dennis W. Dickson; Keith A. Josephs; Jennifer L. Whitwell

doi:10.1002/ana.25893

Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration

Alma Ghirelli, Nirubol Tosakulwong, Stephen D. Weigand, Heather M. Clark, Farwa Ali, Hugo Botha, Joseph R. Duffy, Rene L. Utianski, Marina Buciuc, Melissa E. Murray, Sydney A. Labuzan, Anthony J. Spychalla, Nha Trang Thu Pham, Christopher G. Schwarz, Matthew L. Senjem, Mary M. Machulda, Matthew Baker, Rosa Rademakers, Massimo Filippi, Clifford R. JackVal J. Lowe, Joseph E. Parisi, Dennis W. Dickson, Keith A. Josephs, Jennifer L. Whitwell

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective: To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer-related pathology and 4-repeat tau pathology in autopsy-confirmed frontotemporal lobar degeneration (FTLD). Methods: Twenty-four patients had [¹⁸F]-flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD-TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)-PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta-ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden. Results: Nine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty-one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta-ROI SUVRs were not elevated in Braak IV or primary age-related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions. Interpretation: Molecular PET shows expected correlations with Alzheimer-related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009–1022.

Original language	English (US)
Pages (from-to)	1009-1022
Number of pages	14
Journal	Annals of neurology
Volume	88
Issue number	5
DOIs	https://doi.org/10.1002/ana.25893
State	Published - Nov 1 2020

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Ghirelli, A., Tosakulwong, N., Weigand, S. D., Clark, H. M., Ali, F., Botha, H., Duffy, J. R., Utianski, R. L., Buciuc, M., Murray, M. E., Labuzan, S. A., Spychalla, A. J., Pham, N. T. T., Schwarz, C. G., Senjem, M. L., Machulda, M. M., Baker, M., Rademakers, R., Filippi, M., ... Whitwell, J. L. (2020). Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration. Annals of neurology, 88(5), 1009-1022. https://doi.org/10.1002/ana.25893

Ghirelli, A, Tosakulwong, N, Weigand, SD, Clark, HM , Ali, F , Botha, H, Duffy, JR, Utianski, RL, Buciuc, M, Murray, ME, Labuzan, SA, Spychalla, AJ, Pham, NTT, Schwarz, CG, Senjem, ML, Machulda, MM, Baker, M, Rademakers, R, Filippi, M, Jack, CR , Lowe, VJ, Parisi, JE, Dickson, DW , Josephs, KA & Whitwell, JL 2020, 'Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration', Annals of neurology, vol. 88, no. 5, pp. 1009-1022. https://doi.org/10.1002/ana.25893

@article{376bf59336934892a5d4d07eae2fbb1f,

title = "Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration",

abstract = "Objective: To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer-related pathology and 4-repeat tau pathology in autopsy-confirmed frontotemporal lobar degeneration (FTLD). Methods: Twenty-four patients had [18F]-flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD-TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)-PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta-ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden. Results: Nine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty-one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta-ROI SUVRs were not elevated in Braak IV or primary age-related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions. Interpretation: Molecular PET shows expected correlations with Alzheimer-related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009–1022.",

author = "Alma Ghirelli and Nirubol Tosakulwong and Weigand, {Stephen D.} and Clark, {Heather M.} and Farwa Ali and Hugo Botha and Duffy, {Joseph R.} and Utianski, {Rene L.} and Marina Buciuc and Murray, {Melissa E.} and Labuzan, {Sydney A.} and Spychalla, {Anthony J.} and Pham, {Nha Trang Thu} and Schwarz, {Christopher G.} and Senjem, {Matthew L.} and Machulda, {Mary M.} and Matthew Baker and Rosa Rademakers and Massimo Filippi and Jack, {Clifford R.} and Lowe, {Val J.} and Parisi, {Joseph E.} and Dickson, {Dennis W.} and Josephs, {Keith A.} and Whitwell, {Jennifer L.}",

note = "Publisher Copyright: {\textcopyright} 2020 American Neurological Association",

year = "2020",

month = nov,

day = "1",

doi = "10.1002/ana.25893",

language = "English (US)",

volume = "88",

pages = "1009--1022",

journal = "Annals of neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "5",

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TY - JOUR

T1 - Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration

AU - Ghirelli, Alma

AU - Tosakulwong, Nirubol

AU - Weigand, Stephen D.

AU - Clark, Heather M.

AU - Ali, Farwa

AU - Botha, Hugo

AU - Duffy, Joseph R.

AU - Utianski, Rene L.

AU - Buciuc, Marina

AU - Murray, Melissa E.

AU - Labuzan, Sydney A.

AU - Spychalla, Anthony J.

AU - Pham, Nha Trang Thu

AU - Schwarz, Christopher G.

AU - Senjem, Matthew L.

AU - Machulda, Mary M.

AU - Baker, Matthew

AU - Rademakers, Rosa

AU - Filippi, Massimo

AU - Jack, Clifford R.

AU - Lowe, Val J.

AU - Parisi, Joseph E.

AU - Dickson, Dennis W.

AU - Josephs, Keith A.

AU - Whitwell, Jennifer L.

PY - 2020/11/1

Y1 - 2020/11/1

N2 - Objective: To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer-related pathology and 4-repeat tau pathology in autopsy-confirmed frontotemporal lobar degeneration (FTLD). Methods: Twenty-four patients had [18F]-flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD-TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)-PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta-ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden. Results: Nine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty-one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta-ROI SUVRs were not elevated in Braak IV or primary age-related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions. Interpretation: Molecular PET shows expected correlations with Alzheimer-related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009–1022.

AB - Objective: To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer-related pathology and 4-repeat tau pathology in autopsy-confirmed frontotemporal lobar degeneration (FTLD). Methods: Twenty-four patients had [18F]-flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD-TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)-PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta-ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden. Results: Nine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty-one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta-ROI SUVRs were not elevated in Braak IV or primary age-related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions. Interpretation: Molecular PET shows expected correlations with Alzheimer-related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009–1022.

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DO - 10.1002/ana.25893

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AN - SCOPUS:85090762930

SN - 0364-5134

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SP - 1009

EP - 1022

JO - Annals of neurology

JF - Annals of neurology

IS - 5

ER -

Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration

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