Performance of [18F]RO948 PET, MRI and CSF neurofilament light in the differential diagnosis of progressive supranuclear palsy.

INTRODUCTION:The diagnosis of progressive supranuclear palsy (PSP) is often challenging since PSP may clinically resemble other neurodegenerative disorders. Recently, the tau PET tracer [18F]RO948, a potential new biomarker for PSP, was developed. The aim of this study was to determine the ability of three different biomarkers, including [18F]RO948 PET, to distinguish PSP patients from healthy controls and from patients with α-synucleinopathies. METHODS:Patients with PSP (n = 23), α-synucleinopathies (n = 47) and healthy controls (n = 61) were included from the BioFINDER-2 study. [18F]RO948 standardized uptake value ratios (SUVR), magnetic resonance imaging midbrain/pons ratio, and cerebrospinal fluid neurofilament light (NfL) levels were compared between diagnostic groups individually and in combination. RESULTS:[18F]RO948 PET SUVR in the globus pallidus, NfL, and midbrain/pons area ratios were all able to differentiate PSP patients from controls and from patients with α-synucleinopathies ([18F]RO948 [mean ± SD]: controls 1.24 ± 0.22; PSP 1.47 ± 0.4; PD 1.18 ± 0.2; DLB 1.25 ± 0.24, p < 0.05), (NfL pg/mL [mean ± SD]: controls 1055 ± 569; PSP 2197 ± 1010; PD 1038 ± 416; DLB 1548 ± 687, p < 0.001) and (midbrain/pons ratio [mean ± SD]: controls 0.46 ± 0.07; PSP 0.34 ± 0.09; PD 0.43 ± 0.06; DLB 0.40 ± 0.07, p < 0.01). Receiver operating characteristic (ROC) analyses indicated that combining the three biomarkers resulted in the highest area under the ROC values (0.94 [0.88-1.00]) for separating controls from PSP and (0.92 [0.85-0.99]) for separating PSP from α-synucleinopathies. CONCLUSIONS:All studied biomarkers could individually separate PSP from controls and α-synucleinopathies patients at a group level. The optimal prediction models included NfL and midbrain/pons ratio for separating controls from PSP and all three biomarkers for separating PSP from α-synucleinopathies.