Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer's disease

Abstract

Background: The Centiloid scale was developed to standardise the results of beta-amyloid (Aβ) PET. We aimed to determine the Centiloid unit (CL) thresholds for CERAD sparse and moderate-density neuritic plaques, Alzheimer's disease neuropathologic change (ADNC) score of intermediate or high probability of Alzheimer's Disease (AD), final clinicopathological diagnosis of AD, and expert visual read of a positive Aβ PET scan. Methods: Aβ PET results in CL for 49 subjects were compared with post-mortem findings, visual read, and final clinicopathological diagnosis. The Youden Index was used to determine the optimal CL thresholds from receiver operator characteristic (ROC) curves. Results: A threshold of 20.1 CL (21.3 CL when corrected for time to death, AUC 0.97) yielded highest accuracy in detecting moderate or frequent plaque density while < 10 CL was optimal for excluding neuritic plaque. The threshold for ADNC intermediate or high likelihood AD was 49.4 CL (AUC 0.98). Those cases with a final clinicopathological diagnosis of AD yielded a median CL result of 87.7 (IQR ± 42.2) with 94% > 45 CL. Positive visual read agreed highly with results > 26 CL. Conclusions: Centiloid values < 10 accurately reflected the absence of any neuritic plaque and > 20 CL indicated the presence of at least moderate plaque density, but approximately 50 CL or more best confirmed both neuropathological and clinicopathological diagnosis of Alzheimer's disease.