In Vivo Imaging and Autoradiography in a Case of Autopsy-Confirmed Pick Disease

Utianski, Rene L.; Schwarz, Christopher G.; Murray, Melissa E.; Tranovich, Jessica F.; Scott, Nancy; Lowe, Val J.; Whitwell, Jennifer L.; Josephs, Keith A.

doi:10.1212/cpj.0000000000000755

Cited by 4 publications

(6 citation statements)

References 7 publications

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“…Furthermore, flortaucipir studies have shown elevated uptake in patients that are presumed to have FTLD, including semantic dementia (presumed TDP‐43), 22,23 as well as PSP, 24,25 corticobasal syndrome (CBS), 21,26 and progressive apraxia of speech (presumed 4R tau) 27 . We have shown flortaucipir uptake in frontotemporal lobes of a patient with autopsy‐confirmed Pick disease 28 . These findings have been consistently observed despite that autoradiographic studies have found little or no binding of flortaucipir to TDP‐43, 3R tau, or 4R tau, 8–10 raising the question of whether the ligand is binding to some off‐target material.…”

Section: Introductionmentioning

confidence: 74%

“…29,30 We have also previously reported significant correlations between tau burden and flortaucipir in our case of Pick disease, a 3R tauopathy. 28 It is clear, however, that further work is needed to fully understand the pathological correlates of flortaucipir in 4R and 3R tauopathies.…”

Section: Discussionmentioning

confidence: 99%

“…The 24 patients had been evaluated between July 1, 2015 and October 10, 2019. Of these 24, autopsy diagnoses were PSP in 10, CBD in 10, FTLD‐TDP type A in 3, and Pick disease in 1 (this case has been previously published) 28 . All 3 FTLD‐TDP patients were tested for mutations in the progranulin gene ( GRN ), and 1 was found to have a GRN mutation.…”

Section: Methodsmentioning

confidence: 99%

“…Of these 24, autopsy diagnoses were PSP in 10, CBD in 10, FTLD-TDP type A in 3, and Pick disease in 1 (this case has been previously published). 28 All 3 FTLD-TDP patients were tested for mutations in the progranulin gene (GRN), and 1 was found to have a GRN mutation. All participants underwent longitudinal neurologic, neuropsychologic, and speech/language evaluations.…”

Section: Participant Cohortmentioning

confidence: 99%

“…27 We have shown flortaucipir uptake in frontotemporal lobes of a patient with autopsy-confirmed Pick disease. 28 These findings have been consistently observed despite that autoradiographic studies have found little or no binding of flortaucipir to TDP-43, 3R tau, or 4R tau, [8][9][10] raising the question of whether the ligand is binding to some offtarget material. Single case studies have shown that flortaucipir uptake correlates with tau burden across brain regions in CBD, 29,30 although no large PET autopsy study has evaluated the degree to which flortaucipir relates to underlying tau burden in FTLD.…”

Section: Introductionmentioning

confidence: 97%

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

Ghirelli

Tosakulwong

Weigand

et al. 2020

Annals of Neurology

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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 [ 18 F]-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.

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Section: Introductionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Participant Cohortmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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

Ghirelli

Tosakulwong

Weigand

et al. 2020

Annals of Neurology

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Tau Imaging in Neurodegenerative Dementia

Ponisio

Iranpour

Benzinger

2021

Hybrid PET/MR Neuroimaging

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Overview of tau PET molecular imaging

Petersen

Roytman

Chiang

et al. 2022

Current Opinion in Neurology

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Purpose of reviewThis article reviews tau PET imaging with an emphasis on first-generation and second-generation tau radiotracers and their application in neurodegenerative disorders, including Alzheimer's disease and non-Alzheimer's disease tauopathies. Recent findingsTau is a critical protein, abundant in neurons within the central nervous system, which plays an important role in maintaining microtubules by binding to tubulin in axons. In its abnormal hyperphosphorylated form, accumulation of tau has been linked to a variety of neurodegenerative disorders, collectively referred to as tauopathies, which include Alzheimer's disease and non-Alzheimer's disease tauopathies [e.g., corticobasal degeneration (CBD), argyrophilic grain disease, progressive supranuclear palsy (PSP), and Pick's disease]. A number of first-generation and second-generation tau PET radiotracers have been developed, including the first FDA-approved agent [ 18 F]-flortaucipir, which allow for in-vivo molecular imaging of underlying histopathology antemortem, ultimately guiding disease staging and development of disease-modifying therapeutics. SummaryTau PET is an emerging imaging modality in the diagnosis and staging of tauopathies.

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In Vivo Imaging and Autoradiography in a Case of Autopsy-Confirmed Pick Disease

Cited by 4 publications

References 7 publications

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

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

Tau Imaging in Neurodegenerative Dementia

Overview of tau PET molecular imaging

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