Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer's Disease Spectrum: Who Really Deserves an A+?

• Published in: Journal of Alzheimer's disease Vol. 85; no. 3; p. 1009
• Main Authors: Sacchi, Luca, Carandini, Tiziana, Fumagalli, Giorgio Giulio, Pietroboni, Anna Margherita, Contarino, Valeria Elisa, Siggillino, Silvia, Arcaro, Marina, Fenoglio, Chiara, Zito, Felicia, Marotta, Giorgio, Castellani, Massimo, Triulzi, Fabio, Galimberti, Daniela, Scarpini, Elio, Arighi, Andrea
• Format: Journal Article
• Language: English
• Published: Netherlands 2022
• Subjects: Aged; Alzheimer Disease - cerebrospinal fluid; Amyloid; Amyloid beta-Peptides; Biomarkers - cerebrospinal fluid; Female; Humans; Magnetic Resonance Imaging; Male; Peptide Fragments; Positron-Emission Tomography; Retrospective Studies; tau Proteins - cerebrospinal fluid; Florbetaben; amyloid; Alzheimer’s disease; standardized uptake value ratio; amyloid-PET; biomarkers; cerebrospinal fluid; Aβ42/40 ratio; centiloids; tau
• ISSN: 1875-8908
• DOI: 10.3233/JAD-210593

Association between cerebrospinal fluid (CSF)-amyloid-β (Aβ)42 and amyloid-PET measures is inconstant across the Alzheimer's disease (AD) spectrum. However, they are considered interchangeable, along with Aβ42/40 ratio, for defining 'Alzheimer's Disease pathologic change' (A+).
Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients.
We included 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of Aβ42 within a 365-days interval. Thresholds used for dichotomization were: Aβ42 < 640 pg/mL (Aβ42+); pTau > 61 pg/mL (pTau+); and Aβ42/40 < 0.069 (ADratio+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC).
Different pipelines gave highly inter-correlated standardized uptake value ratios (SUVRs) (rho = 0.93-0.99). The most significant findings were: pTau positive correlation with SPMCL SUVR (rho = 0.56, p = 0.0063) and Aβ42/40 negative correlation with SPMCL and SPMAAL SUVRs (rho = -0.56, p = 0.0058; rho = -0.52, p = 0.0117 respectively). No correlations between CSF-Aβ42 and global SUVRs were observed. In subregion analysis, both pTau and Aβ42/40 values significantly correlated with cingulate SUVRs from any pipeline (R2 = 0.55-0.59, p < 0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for Aβ42/40 ratio were still significant in linear regression models. Moreover, combining pTau with Aβ42 or using Aβ42/40, instead of Aβ42 alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids.
We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-Aβ42/40 and secondarily pTau rather than Aβ42 levels.