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 [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. ANN NEUROL 2020;88:1009-1022.

• Authors: 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 Jr, Val J Lowe, Joseph E Parisi, Dennis W Dickson, Keith A Josephs, Jennifer L Whitwell
• Journal: Annals of neurology (Ann Neurol) Vol. 88 Issue 5 Pg. 1009-1022 (11 2020) ISSN: 1531-8249 [Electronic] United States
• PMID: 32869362 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Neurological Association.

Chemical References

• Amyloid beta-Peptides
• Carbolines
• MAPT protein, human
• Radiopharmaceuticals
• tau Proteins
• 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (diagnostic imaging, pathology)
• Amyloid beta-Peptides (metabolism)
• Autopsy
• Autoradiography
• Carbolines
• Cohort Studies
• Female
• Frontotemporal Lobar Degeneration (diagnostic imaging, pathology)
• Humans
• Male
• Mesencephalon (diagnostic imaging, pathology)
• Middle Aged
• Neurofibrillary Tangles (pathology)
• Positron-Emission Tomography
• Radiopharmaceuticals
• Red Nucleus (diagnostic imaging, pathology)
• Sensitivity and Specificity
• tau Proteins (metabolism)