Neuroinflammation and flortaucipir PET in non‐fluent/agrammatic variant of primary progressive aphasia and/or apraxia of speech

Abstract

Background: Neuroinflammation, a hallmark of frontotemporal dementia, has been sparsely studied in vivo. However, neuroinflammation is a potentially important therapeutic target and biomarkers of inflammation would be welcome. To determine the anatomical specificity of a putative biomarker for inflammation, translocator protein 18 kDa (TSPO) imaging, we used 11 C-PBR28 PET to measure TSPO levels in patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and/or apraxia of speech (AOS).Methods: Sixteen patients with nfvPPP/AOS underwent PET using 11 C-PBR28 and 18 Fflortaucipir. All patients were PET amyloid-negative except two, with a non-AD flortaucipir PET. Thirty healthy controls underwent PET imaging using 11 C-PBR28 (13 controls) or 18 F-flortaucipir (17 controls). Patients (9/16 women, mean age 65±5.9 years) did not differ significantly in age from the controls (17/30 women, mean age 66±9.3 years). V T values for 11 C-PBR28 were calculated with the Logan plot and a metabolitecorrected arterial input function. For 18 F-flortaucipir, the SUV ratio over the cerebellar gray matter was calculated for t = 80-100 min. All images were corrected for partial volume effect. A full factorial analysis was performed on V T and SUVR values between patients and controls at the voxel-wise level.Results: Compared to controls, patients showed increased V T and SUVR values (p < 0.001 uncorrected) in left inferior, middle and superior frontal gyri, as well as in the left putamen and pallidum. However, peak uptake of 18 F-flortaucipir was localized in Broca's area, epicenter of the pathology, while the distribution of 11 C-PBR28 V T was more extensive in the frontal lobe, including precentral gyrus, and other regions outside of the frontal lobe, as the supramarginal gyrus and superior temporal sulcus, as well as a small area in the posterior extent of the right inferior frontal gyrus.Conclusions: 11 C-PBR28 and 18 F-flortaucipir uptake patterns corresponded to anatomical areas known to be related to the specific language functions that are impaired in nfvPPA and apraxia of speech. Thus, 11 C-PBR28 seems to be a suitable radioligand for detecting neuroinflammation in nfvPPA. Furthermore, the more exten-