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INTRODUCTION: We sought to establish the relationships between standard post mortem measures of AD neuropathology and ante mortem [(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, 92 CL for frequent plaques) and non-linearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. Findings were comparable across sites and when restricted to 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (AUC=0.910, Sensitivity=89.2%, Specificity=86.4%) while 24.4 CL identified intermediate-to-high AD neuropathological changes (AUC=0.894, Sensitivity=84.1%, Specificity=87.9%). DISCUSSION: Our study demonstrated the robustness of a multi-site Centiloid [(11)C]PIBPET study and established a range of pathology-based CL thresholds.

Hippocampal atrophy is a marker of disease state and progression in Alzheimer's disease. The gold standard to measure hippocampal volume is through manual segmentation. A number of protocols to measure hippocampal volume through manual segmentation have been developed, but the marked heterogeneity of anatomical landmarks has given rise to wide variability of volume estimates. With the aim of fostering the use of hippocampal volume in routine clinical settings, an international task force is currently working on developing a harmonized protocol that will resolve and reduce the present heterogeneity. The task force will then validate the harmonized protocol, develop harmonized probabilistic hippocampal maps, and develop illustrative and educational material on the use of the harmonized protocol and maps.