Background: Association between cerebrospinal fluid (CSF)-amyloid-beta (A beta)(42) and amyloid-PET measures is inconstant across the Alzheimer's disease (AD) spectrum. However, they are considered interchangeable, along with A beta(42/40) ratio, for defining 'Alzheimer's Disease pathologic change' (A+).Objective: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients.Methods: We included 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of A beta(42) within a 365-days interval. Thresholds used for dichotomization were: A beta(42) < 640 pg/mL (A beta(42)+); pTau > 61 pg/mL (pTau+); and A beta(42/40) < 0.069 (AD(ratio)+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC).Results: 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 A beta(42/40) negative correlation with SPMCL and SPMAAL SUVRs (rho = -0.56, p = 0.0058; rho = -0.52, p = 0.0117 respectively). No correlations between CSF-A beta(42) and global SUVRs were observed. In subregion analysis, both pTau and A beta 6(42/40) values significantly correlated with cingulate SUVRs from any pipeline (R-2 = 0.55-0.59, p < 0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for A beta(42/40) ratio were still significant in linear regression models. Moreover, combining pTau with A beta(42) or using A beta(42/40), instead of A beta(42) alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids.Conclusion: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-A beta(42/40) and secondarily pTau rather than A beta(42) levels.

Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer's Disease Spectrum: Who Really Deserves an A+? / L. Sacchi, T. Carandini, G.G. Fumagalli, A.M. Pietroboni, V.E. Contarino, S. Siggillino, M. Arcaro, C. Fenoglio, F. Zito, G. Marotta, M. Castellani, F. Triulzi, D. Galimberti, E. Scarpini, A. Arighi. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 85:3(2022), pp. 1009-1020. [10.3233/JAD-210593]

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

L. Sacchi
Primo
;
T. Carandini;G.G. Fumagalli;A.M. Pietroboni;M. Arcaro;C. Fenoglio;M. Castellani;F. Triulzi;D. Galimberti;E. Scarpini
Penultimo
;
A. Arighi
2022

Abstract

Background: Association between cerebrospinal fluid (CSF)-amyloid-beta (A beta)(42) and amyloid-PET measures is inconstant across the Alzheimer's disease (AD) spectrum. However, they are considered interchangeable, along with A beta(42/40) ratio, for defining 'Alzheimer's Disease pathologic change' (A+).Objective: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients.Methods: We included 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of A beta(42) within a 365-days interval. Thresholds used for dichotomization were: A beta(42) < 640 pg/mL (A beta(42)+); pTau > 61 pg/mL (pTau+); and A beta(42/40) < 0.069 (AD(ratio)+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC).Results: 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 A beta(42/40) negative correlation with SPMCL and SPMAAL SUVRs (rho = -0.56, p = 0.0058; rho = -0.52, p = 0.0117 respectively). No correlations between CSF-A beta(42) and global SUVRs were observed. In subregion analysis, both pTau and A beta 6(42/40) values significantly correlated with cingulate SUVRs from any pipeline (R-2 = 0.55-0.59, p < 0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for A beta(42/40) ratio were still significant in linear regression models. Moreover, combining pTau with A beta(42) or using A beta(42/40), instead of A beta(42) alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids.Conclusion: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-A beta(42/40) and secondarily pTau rather than A beta(42) levels.
Alzheimer’s disease; Aβ42/40 ratio; Florbetaben; amyloid; amyloid-PET; biomarkers; centiloids; cerebrospinal fluid; standardized uptake value ratio; tau; Aged; Alzheimer Disease; Biomarkers; Female; Humans; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Retrospective Studies; tau Proteins; Amyloid; Amyloid beta-Peptides; Peptide Fragments
Settore BIO/13 - Biologia Applicata
2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/943379
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