HAI Book 2025 - Flipbook - Page 178
Gatto, Rodolfo
32
An assessment of the utility of flortaucipir PET to detect four-repeat
tau pathology in a globular glia tauopathy case-series
Rodolfo Gatto1, Hossam Youssef1, Sujala Ghatamaneni3, Gokhan Uruk1, Paul Min3, Mu-Hui Fu1,
R. Ross Reichard2, Val Lowe3, Dennis Dickson4, Jennifer Whitwell3, Keith Josephs1
1
Department of Neurology, Mayo Clinic, Rochester, MN, US
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, US
3
Department of Radiology, Mayo Clinic, Rochester, MN, US
4
Department of Neuropathology, Mayo Clinic, Jacksonville, FL, US
2
Introduction: Glial globular tauopathy (GGT) represents a rare neuropathological form of frontotemporal lobar
degeneration characterized by four-repeat tau-positive astrocytic and globular glial inclusions. However, little is
known about antemortem tau-PET imaging in GGT and whether tau-PET can detect four-repeat tau inclusions in
GGT.
Objective: To investigate whether uptake is observed on antemortem tau-PET, using the flortaucipir ligand, in
patients with GGT and determine whether uptake represents underlying four-repeat tau or other
neuropathological targets.
Materials and Methods: Three patients with neuropathologically confirmed GGT who underwent antemortem
flortaucipir PET were investigated. Neuropathological analyses focused on grey and white matter (GM & WM) from
the superior medial frontal gyrus (S/M-MG) and superior lateral temporal gyrus (S/L-TG). Immunohistochemical
staining was performed with antibodies to tau (AT8, PHF-1, RD4), astrocytic glial fibrillary acidic protein (GFAP),
and microglia (Iba1). Beta-amyloid was assessed with Thioflavin-T. Flortaucipir binding was indirectly assessed
using a histopathological fluorescent flortaucipir analog (T726). Regional standard uptake value ratios (SUVRs)
were calculated from premortem tau-PET images matched to the neuropathological region. Autoradiography
studies with a flortaucipir radioligand were performed on consecutive slides.
Results: In all three GGT cases, T726 colocalization was observed in WM than in GM. In WM, T726 colocalization
was greatest with PHF-1, followed by RD4 and GFAP, and minimal with Iba1. Elevated antemortem tau-PET SUVRs
were observed in S/M-FG and S/L-TG WM regions in all GGT cases. In-vitro flortaucipir autoradiography studies
demonstrated no binding to tau in GM or WM.
Conclusions: Although autoradiographic findings were negative, there is some evidence that flortaucipir PET
uptake in GGT represents an underlying four-repeat tau burden, especially in the WM.
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