Multisite study of the relationships between antemortem [ ¹¹ C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology

Introduction: We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [ ¹¹ C]PIB–positron emission tomography ([ ¹¹ C]PIB-PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification. Methods: Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings. Results: CL values increased with each CERAD neuritic plaque score increment (median −3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET-pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate-to-high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%). Discussion: Our study demonstrated the robustness of a multisite Centiloid [ ¹¹ C]PIB-PET study and established a range of pathology-based CL thresholds.