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

• Published in: Alzheimer's research & therapy Vol. 12; no. 1; p. 22
• Main Authors: Amadoru, Sanka, Doré, Vincent, McLean, Catriona A, Hinton, Fairlie, Shepherd, Claire E, Halliday, Glenda M, Leyton, Cristian E, Yates, Paul A, Hodges, John R, Masters, Colin L, Villemagne, Victor L, Rowe, Christopher C
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.03.2020; BioMed Central; BMC
• Subjects: Advertising executives; Aged; Alzheimer Disease - diagnosis; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - analysis; Amyloid beta-protein; Amyloid imaging; Biomarkers; Brain - pathology; Brain research; Centiloids; Dementia; Development and progression; Diagnosis; Diagnostic imaging; Diseases; Female; Florbetapir; Flutemetamol; Health aspects; Humans; Male; Measurement; Medical research; Neuropathology; Plaque, Amyloid - diagnosis; Plaque, Amyloid - pathology; Positron emission tomography; Positron-Emission Tomography - methods; Radiopharmaceuticals; Software; Telecommunications equipment; Time; Tomography; Australia; Centiloids; Alzheimer’s disease; Neuropathology; Positron emission tomography; Amyloid imaging
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-020-00587-5

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. 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. 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. 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.