Additional file 1 of Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease
Creators: name: Guo, Tengfei
name: Korman, Deniz
name: Joie, Renaud La
name: Shaw, Leslie M.
name: Trojanowski, John Q.
name: Jagust, William J.
name: Landau, Susan M.
Publisher: name: figshare
Year: 2020
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Neuroscience
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: Cancer
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: Hematology
subject: 110309 Infectious Diseases
subject: Computational Biology

description: Additional file 1: Figure S1. The ROC analysis using the Youden index classifying 280 Aβ- ADNI cognitively unimpaired (CU) participants and 183 Aβ + ADNI MCI and AD patients as the endpoint to define the cutoff ≥1.25 for Temporal-metaROI FTP SUVR. AUC: 0.876 (95%CI, 0.84, 0.912). Among these 463 ADNI participants, 217 (47%) participants were included in the analyses of the manuscript. Figure S2. Histograms of Temporal-metaROI FTP SUVRs of (A) all 775 ADNI participants, (B) 280 Aβ- ADNI CU participants and (C) 183 Aβ + ADNI MCI and AD patients with tau PET scan. Red dotted line is the cutoff of Temporal-metaROI FTP SUVR 1.25. Figure S3. The ROC analysis using the Youden index classifying 280 Aβ- ADNI CU participants and 183 Aβ + ADNI MCI and AD patients as the endpoint to define the cutoff ≥1.21 for entorhinal FTP SUVR. AUC: 0.891 (95%CI, 0.856, 0.926). Figure S4. Histograms of entorhinal FTP SUVRs of (A) all 775 ADNI participants, (B) 280 Aβ- ADNI CU participants and (C) 183 Aβ + ADNI MCI and AD patients with tau PET scan. Red dotted line is the cutoff of entorhinal FTP SUVR 1.21. Figure S5. The ROC analysis using the Youden index classifying 320 Aβ- ADNI CU participants and 429 Aβ + ADNI MCI and AD patients as the endpoint to define the cutoff ≥22 for CSF p-Tau. AUC: 0.865 (95%CI, 0.84, 0.89). Among these 749 ADNI participants, 212 (28%) participants were included in the analyses of the manuscript. Figure S6. Histograms of CSF p-Tau of (A) all 1534 ADNI participants, (B) 320 Aβ- ADNI CU participants and (C) 429 Aβ + ADNI MCI and AD patients with CSF p-Tau measurement. Red dotted line is the cutoff of CSF p-Tau 22. Figure S7. The ROC analysis using the Youden index classifying 169 Aβ- ADNI CU participants and 160 Aβ + ADNI MCI and AD patients as the endpoint to define the cutoff ≥0.0012 for CSF p-Tau/Aβ40 ratio. AUC: 0.976 (95%CI, 0.96, 0.99). Among these 329 ADNI participants, 201 (61%) participants were included in the analyses of the manuscript. Figure S8. Histograms of CSF p-Tau/Aβ40 for (A) all 447 ADNI participants, (B) 169 Aβ- ADNI CU participants and (C) 160 Aβ + ADNI MCI and AD patients with CSF p-Tau/Aβ40. Red dotted line is the 0.0012 cutoff for the CSF p-Tau/Aβ40 ratio. Figure S9. Cross-sectional associations between CSF MASS Aβ42 and CSF p-Tau. The vertical gray dashed line reflects the abnormal threshold of CSF p-Tau. Abbreviations: p-Tau = phosphorylated tau; Aβ = amyloid-β; CU = cognitively unimpaired; MCI = mild cognitive impairment; AD = Alzheimer’s disease. Figure S10. Regions with significant association between CSF P-tau and FTP tau in (A) Aβ+, (B) CU and (C) non-demented participants. Abbreviations: Spearman rho = Spearman’s correlation coefficient; p-Tau = phosphorylated tau; Aβ = amyloid-β; FTP = 18F-flortaucipir; SUVR = standardized uptake value ratio; CU = cognitively unimpaired; MCI = mild cognitive impairment; AD = Alzheimer’s disease. Figure S11. Cross-sectional associations between Aβ PET, CSF p-Tau/Aβ40 and entorhinal tau PET. (A). Associations between baseline entorhinal tau PET and Aβ PET. Associations between baseline CSF p-Tau/Aβ40 and entorhinal tau PET in the whole cohort (B), Aβ- (C) and Aβ + (D) participants. The vertical and horizontal gray dashed lines reflect the abnormal thresholds of corresponding biomarkers in x-axis and y-axis respectively. Abbreviations: Aβ = amyloid-β; A = Aβ PET; − = negative; + = positive; AD = Alzheimer’s disease; CU = cognitively unimpaired; FTP = 18F-flortaucipir; MCI = mild cognitive impairment. Figure S12. Cross-sectional associations between Aβ PET, CSF pTau/Aβ40 and tau PET using alternative cutoffs. Associations between baseline Aβ PET and (A) CSF pTau, (B) CSF pTau/Aβ40 and (C) temporal tau PET. Associations between baseline CSF pTau and CSF pTau/Aβ40 in the whole cohort (D), Aβ- (E) and Aβ + (F) participants. Associations between baseline CSF pTau/Aβ40 and Temporal-metaROI tau PET in the whole cohort (G), Aβ- (H) and Aβ + (I) participants. The vertical and horizontal gray dashed lines reflect the abnormal thresholds of corresponding biomarkers in x-axis and y-axis respectively. Abbreviations: Aβ = amyloid-β; A = Aβ PET; − = negative; + = positive; AD = Alzheimer’s disease; CU = cognitively unimpaired; FTP = 18F-flortaucipir; MCI = mild cognitive impairment; pTau = phosphorylated tau; PTAU = CSF pTau or CSF pTau/Aβ40 ratio; SUVR = standardized uptake value ratio; T = CSF pTau or CSF pTau/Aβ40 or tau PET. Figure S13. Cross-sectional associations between Aβ PET, CSF p-Tau/Aβ40 and entorhinal tau PET using alternative cutoffs. (A). Associations between baseline entorhinal tau PET and Aβ PET. Associations between baseline CSF p-Tau/Aβ40 and entorhinal tau PET in the whole cohort (B), Aβ- (C) and Aβ + (D) participants. The vertical and horizontal gray dashed lines reflect the abnormal thresholds of corresponding biomarkers in x-axis and y-axis respectively. Abbreviations: Aβ = amyloid-β; A = Aβ PET; − = negative; + = positive; AD = Alzheimer’s disease; CU = cognitively unimpaired; FTP = 18F-flortaucipir; MCI = mild cognitive impairment.