A)Blood Sample Collection and Analysis: AIBL

1.SUPPLEMENTARY METHODS

a)Blood Sample Collection and Analysis: AIBL

Whole blood (80 mL) was collected in the morning (after overnight fasting) by venepuncture, filled tubes were inverted several times and incubated on a laboratory orbital shaker for approximately 15 minutes at room temperature prior to being fractionated. A subset of blood tubes were sent (Melbourne Health, Melbourne, Victoria; PathWest Laboratory Medicine, Perth, Western Australia) for full blood pathology testing.

For plasma preparation, whole blood was spun at 200 x g, at 20°C, for 10 minutes with no brake. The resulting supernatant (platelet rich plasma) was transferred to new 15 mL tubes and 5 mm margins were left at the interface to ensure that the red blood cell pellets were not disturbed. The platelet rich plasma was then spun at 800 x g at 20°C for 15 minutes with the brake on, to obtain the platelet depleted plasma. The platelet depleted plasma, was aliquotted into 1 mL Nunc cryobank polypropylene tubes (Thermo Scientific) and immediately transferred to a rack on dry ice before long term storage in liquid nitrogen vapour tanks.

b)Cohort Details: Alzheimer’s Disease Neuroimaging Initiative

The Data used in the preparation of this article were obtained from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). The ADNI was launched in 2003 by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Food and Drug Administration (FDA), private pharmaceutical companies and non-profit organizations, as a $60 million, 5-year public-private partnership. The primary goal of ADNI has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD). Determination of sensitive and specific markers of very early AD progression is intended to aid researchers and clinicians to develop new treatments and monitor their effectiveness, as well as lessen the time and cost of clinical trials.

The Principal Investigator of this initiative is Michael W. Weiner, MD, VA Medical Center and University of California – San Francisco. ADNI is the result of efforts of many co-investigators from a broad range of academic institutions and private corporations, and subjects have been recruited from over 50 sites across the U.S. and Canada. The initial goal of ADNI was to recruit 800 adults, ages 55 to 90, to participate in the research, approximately 200 cognitively normal older individuals to be followed for 3 years, 400 people with MCI to be followed for 3 years and 200 people with early AD to be followed for 2 years. Details on ADNI, particularly sample collection and analysis are reported elsewhere1-3 and for up-to-date information refer to

c)Statistical Software

Analyses were performed using R statistical software package4. Imputations of missing data were performed using multiple imputations by chain equations (mice)5. The univariate and multiple regression analysis used the rms6, car7 and MASS8 packages. Random Forest variable selection and prediction models were performed using the package randomForest9 with all software default settings. SVM/R was performed with the e1071 package10. Receiver operating characteristics (ROC), sensitivities, specificities, accuracies and area under the curve (AUC) values were calculated using ROCR11. Figures represented in this manuscript were generated using the ggplot212 and effects13 packages.

2.SUPPLEMENTARY TABLES

Supplementary Table 1.The age, gender, site and APOEε4 carrier status adjusted marginal means (sd) [median (min - max)] for the low PiB loaders (< 1.3 SUVR) and the high PiB loaders (>= 1.3 SUVR) for A: analytes from the RBM panel, B: analytes from the standard clinical pathology panel C: analytes from metalomic panel, D: plasma APOE measurements and E: plasma Aβ measurements. The p value is the ANCOVA p-value and the adjusted (adj) p-value is adjusted for False Discovery Rate. The following analyteswere removed from the data set due having >5% of their measurements missing; S100B, IL12B, IL11, IL7, GSTM1, CALCA, CTGF, IL23A, IL2, IL6, MMP3, XCL1, EREG, CSF2, F3, IL1A, AGRP, MUC16, LTA, IL1B, NARG1, FGF2, CCL7, EDN1, CCL26, FGF4, NGF, CNTF, SCT, TGFB3, EPO, PYY, IFNG, FABP3, POMC, AREG, TGFA, TNF, IGF1.

A: The RBM Panel
Analyte / Low NAB [mean (SD) / High NAB [mean (SD) / Raw p / Adj p
Adiponectin / 5.02 (3.91) / 4.86 (3.82) / 0.74 / 0.931
Alpha 2 Macroglobulin / 0.91 (0.24) / 0.93 (0.24) / 0.216 / 0.652
Alpha-1-Antitrypsin / 2.35 (0.79) / 2.43 (0.82) / 0.258 / 0.698
Alpha-Fetoprotein / 4.08 (3.91) / 3.44 (3.43) / 0.035 / 0.264
Angiopoietin-2 (ANGPT2) / 8 (4.69) / 8.88 (5.17) / 0.035 / 0.264
Angiotensin-Converting Enzyme / 155.84 (103.51) / 145.16 (96.79) / 0.236 / 0.676
Angiotensinogen / 15.49(10.38 - 23.36) / 21.19(14.01 - 32.51) / 0.08 / 0.415
Apolipoprotein A-I / 0.35 (0.19) / 0.35 (0.19) / 0.822 / 0.954
Apolipoprotein B / 695.20 (373.51) / 705.99 (380.57) / 0.683 / 0.926
Apolipoprotein CIII / 96.72 (61.28) / 93.59 (59.52) / 0.52 / 0.841
Apolipoprotein D / 110.36 (35.99) / 104.67 (34.26) / 0.067 / 0.389
Apolipoprotein E / 44.95 (26.60) / 43.75 (25.99) / 0.549 / 0.856
Apolipoprotein H / 239.29 (91.97) / 239.86 (92.50) / 0.951 / 0.986
AXL Receptor Tyrosine Kinase / 11.25 (4.71) / 12.03 (5.03) / 0.047 / 0.322
Beta-2-Microglobulin / 1.72 (0.68) / 1.81 (0.70) / 0.13 / 0.529
Betacellulin / 187.85 (87.23) / 188.30 (87.73) / 0.985 / 0.991
Bone Morphogenetic Protein 6 / 14.65 (13.01 – 16.38) / 10.75 (10.54 - 10.97) / 0.009 / 0.118
Brain-Derived Neurotrophic Factor / 2.35 (1.93 - 2.84) / 2.24 (2.12 - 2.37) / 0.552 / 0.856
Carcinoembryonic Antigen / 1.63 (1.56) / 1.66 (1.59) / 0.836 / 0.955
CD40 / 0.91 (0.39) / 0.97 (0.40) / 0.071 / 0.399
CD40 Ligand / 0.20 (0.15 - 0.25) / 0.18(0.15 - 0.22) / 0.513 / 0.84
CgA / 511.74 (445.45) / 513.21 (448.25) / 0.9 / 0.975
Chemokine Ligand 13 (CXCL-13) / 22.18 (14.74 - 33.84) / 25.85 (22.85 - 29.41) / 0.093 / 0.45
Complement C3 / 0.85 (0.27) / 0.86 (0.27) / 0.631 / 0.892
Complement Factor H / 2814.06 (1798.43) / 2851.44 (1828.47) / 0.772 / 0.94
Cortisol / 97.51 (44.18) / 103.98 (47.24) / 0.096 / 0.458
C-Reactive Protein (CRP) / 1.84 (2.87) / 1.53 (2.56) / 0.172 / 0.596
Creatine Kinase-MB / 0.44 (0.39) / 0.45 (0.40) / 0.602 / 0.881
Eotaxin / 94.00(80.82 - 110.19) / 93.45(86.12 - 101.83) / 0.931 / 0.983
Epidermal Growth Factor / 49.09(30.99 - 75.68) / 47.45(33.75 - 65.44) / 0.753 / 0.935
Epidermal Growth Factor Receptor / 128.17 (58.33) / 121.38 (55.45) / 0.161 / 0.596
Epithelial-Derived Neutrophil-Activating Protein 78 / 0.51(0.29 - 0.74) / 0.46(0.31 - 0.63) / 0.51 / 0.84
Extracellular Newly Identified Receptor for Advanced Glycation End Products (EN-RAGE) / 4.46 (4.01 - 4.92) / 4.65(4.39 - 4.91) / 0.67 / 0.919
Factor VII / 538.90 (263.69) / 538.15 (264.21) / 0.915 / 0.978
FAS / 7.64 (4.18) / 8.28 (4.51) / 0.09 / 0.44
Fas Ligand / 129.66 (119.41) / 110.39 (102.15) / 0.031 / 0.254
Ferritin / 122.02(113.36 - 130.85) / 136.04(132.35 - 139.65) / 0.311 / 0.755
Fibrinogen / 4.56 (1.94) / 4.62 (1.97) / 0.709 / 0.931
Follicle-Stimulating Hormone / 12.59 (8.55) / 12.56 (8.56) / 0.937 / 0.983
Glucagon / 508.46 (430.98) / 519.5 (441.82) / 0.759 / 0.939
Glucagon-like Peptide 1, total / 31.96 (27.19) / 30.93 (26.42) / 0.618 / 0.883
Granulocyte Colony-Stimulating Factor / 7.21 (6.03) / 7.45 (6.22) / 0.612 / 0.883
Growth Hormone / 1.52(1.20 - 1.91) / 1.31(1.17 - 1.46) / 0.296 / 0.746
Growth-Regulated alpha protein / 303.42(213.69 - 423.2) / 281.77(248.58 - 317.38) / 0.384 / 0.79
Haptoglobin / 1.45 (1.34) / 1.44 (1.33) / 0.862 / 0.957
HCC 4 / 5.16 (3.02) / 5.22 (3.05) / 0.816 / 0.954
Heparin-Binding EGF-Like Growth Factor / 101.08 (75.31) / 90.62 (67.82) / 0.076 / 0.41
Hepatocyte Growth Factor / 2.54 (1.45) / 2.80 (1.56) / 0.043 / 0.307
Immunoglobulin A / 1.39 (1.10) / 1.43 (1.12) / 0.663 / 0.918
Immunoglobulin E / 30.37(20.94 - 43.05) / 31.21 (22.10 - 43.18) / 0.868 / 0.957
Immunoglobulin M (IgM) / 1.01 (0.86) / 0.78 (0.76) / 0.001 / 0.019
Insulin / 1.65 (1.24 - 2.09) / 1.87 (1.53 - 2.24) / 0.211 / 0.648
Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) / 291.98 (253.61) / 335.95 (292.66) / 0.044 / 0.307
Intercellular Adhesion Molecule 1 / 135.74 (52.79) / 132.76 (51.82) / 0.489 / 0.831
Interleukin-1 receptor antagonist / 110.71 (92.31) / 109.84 (91.91) / 0.919 / 0.978
Interleukin-10 / 11.58 (4.90) / 12.23 (5.17) / 0.108 / 0.488
Interleukin-12 Subunit p70 / 56.85 (23.30) / 57.22 (23.52) / 0.818 / 0.954
Interleukin-13 / 102.34 (63.63) / 97.62 (60.93) / 0.436 / 0.818
Interleukin-15 / 0.80 (0.39) / 0.77 (0.38) / 0.408 / 0.805
Interleukin-16 / 429.95 (317.88) / 483.56 (358.63) / 0.058 / 0.365
Interleukin-17 (IL-17) / 31.40 (12.08) / 29.88 (11.56) / 0.13 / 0.529
Interleukin-18 / 225.52 (151.72) / 233.44 (157.56) / 0.528 / 0.847
Interleukin-3 / 0.33 (0.26) / 0.32 (0.26) / 0.559 / 0.861
Interleukin-4 / 59.84 (50.45) / 60.49 (51.16) / 0.861 / 0.957
Interleukin-5 / 7.17 (5.81) / 7.05 (5.75) / 0.908 / 0.978
Interleukin-8 / 10.03 (6.40) / 9.51 (6.12) / 0.322 / 0.756
Leptin / 7.89 (4.46 - 13.14) / 7.07 (4.37 - 10.88) / 0.368 / 0.778
Lipoprotein A / 70.17 (54.73 - 88.79) / 75.69 (63.71 - 90.69) / 0.639 / 0.9
Luteinizing Hormone / 0.73 (0.65) / 0.72 (0.65) / 0.838 / 0.955
Macrophage Colony-Stimulating Factor 1 / 0.73 (0.35) / 0.72 (0.34) / 0.546 / 0.855
Macrophage Inflammatory Protein-1 alpha (MIP1α) / 89.08 (47.39) / 102.97 (54.88) / 0.001 / 0.027
Macrophage Inflammatory Protein-1 beta / 157.92 (153.53) / 147.90 (144.34) / 0.389 / 0.795
Macrophage Migration Inhibitory Factor / 0.37 (0.32) / 0.40 (0.33) / 0.173 / 0.597
Macrophage-Derived Chemokine / 392.14 (158.87) / 377.65 (153.53) / 0.241 / 0.682
Matrix Metalloproteinase-2 / 2432.71 (1455.79) / 2795.02 (1678.17) / 0.006 / 0.093
Matrix Metalloproteinase-9 / 58.55 (48.98 - 70.61) / 58.68 (58.13 - 59.2) / 0.993 / 0.997
Monocyte Chemotactic Protein 1 / 131.81 (99.76) / 132.62 (100.72) / 0.918 / 0.978
Myeloperoxidase / 98.2 (87.81 - 110.44) / 109.85 (100.5 - 120.63) / 0.214 / 0.65
Myoglobin / 16.23 (11.07) / 17.67 (12.03) / 0.136 / 0.54
Neuronal Cell Adhesion Molecule / 2.12 (1.21) / 2.19 (1.24) / 0.503 / 0.836
Pancreatic Polypeptide (PPY) / 130.09 (115.74) / 171.30 (152.65) / < 0.001 / 0.01
Plasminogen Activator Inhibitor-1 / 26.7 (16.76 - 41.26) / 24.77 (19.79 - 30.61) / 0.407 / 0.805
Platelet-Derived Growth Factor BB / 2271.59 (1531.52) / 2278.69 (1541.51) / 0.968 / 0.988
Pregnancy-Associated Plasma Protein A / 0.04 (0.03) / 0.04 (0.03) / 0.247 / 0.683
Prolactin / 8.00 (5.11) / 8.51 (5.42) / 0.308 / 0.755
Prostate-Specific Antigen (free) / 0.39 (0.35 - 0.43) / 0.44 (0.37 - 0.52) / 0.369 / 0.778
Prostatic Acid Phosphatase / 0.26 (0.20) / 0.26 (0.20) / 0.819 / 0.954
Pulmonary and Activation-Regulated Chemokine / 28.56 (11.33) / 29.57 (11.76) / 0.336 / 0.756
Regulated on Activation, Normal T Expressed and Secreted / 4.36 (2.77 - 6.50) / 3.70 (3.18 - 4.26) / 0.116 / 0.507
Resistin / 2.72 (1.62) / 2.91 (1.71) / 0.202 / 0.628
Serum Amyloid P-Component / 22.31 (11.14) / 21.20 (10.64) / 0.209 / 0.645
Serum Glutamic Oxaloacetic Transaminase / 14.07 (4.47) / 14.64 (4.65) / 0.156 / 0.588
Sex Hormone-Binding Globulin / 45.91 (31.02) / 41.32 (28.08) / 0.088 / 0.436
Soluble Receptor for Advanced Glycation Endproducts / 3.58 (2.97) / 3.40 (2.86) / 0.416 / 0.805
Sortilin / 5.85 (2.08) / 5.96 (2.12) / 0.604 / 0.881
Stem Cell Factor / 290.26 (142.56) / 285.13 (140.52) / 0.699 / 0.931
Superoxide Dismutase 1, soluble / 49.13 (35.88) / 53.26 (38.97) / 0.191 / 0.616
T Lymphocyte-Secreted Protein I-309 / 296.64(268.38 - 329.59) / 23875(185.56 - 307.99) / 0.168 / 0.596
Tenascin-C / 1236.13 (917.11) / 1333.57 (992.70) / 0.217 / 0.652
Testosterone / 1.25 (0.65) / 1.36 (0.68) / 0.052 / 0.339
Thrombopoietin / 1.99 (1.41) / 1.87 (1.36) / 0.294 / 0.743
Thrombospondin-1 / 3201.74 (2638.15 - 3848.25) / 2603.17 (2457.76 - 2747.21) / 0.076 / 0.411
Thymus-Expressed Chemokine / 56.79 (43.32) / 57.27 (43.82) / 0.882 / 0.964
Thyroid-Stimulating Hormone / 1.64 (1.64) / 1.67 (1.66) / 0.878 / 0.961
Thyroxine-Binding Globulin / 46.33 (14.28) / 46.21 (14.29) / 0.886 / 0.966
Tissue Inhibitor of Metalloproteinases 1 / 86.87 (28.74) / 87.54 (29.06) / 0.797 / 0.951
TNF-Related Apoptosis-Inducing Ligand Receptor 3 / 9.39 (6.05) / 10.38 (6.66) / 0.061 / 0.372
Tumor necrosis factor receptor 2 / 4.80 (2.16) / 5.16 (2.31) / 0.046 / 0.317
Vascular Cell Adhesion Molecule-1 (VCAM-1) / 609.91 (207.95) / 676.35 (231.34) / <0.001 / 0.01
Vascular Endothelial Growth Factor / 470.27 (240.51) / 495.61 (254.29) / 0.246 / 0.683
von Willebrand Factor / 27.96 (26.98) / 30.55 (29.49) / 0.242 / 0.682
B: The Standard Clinical Pathology Panel
Analyte / Low NAB [mean (SD) / High NAB [mean (SD) / Raw p / Adj p
Alanine Aminotransferase / 20.80 (11.47) / 21.37 (12.15) / 0.596 / 0.845
Albumin / 42.88 (4.20) / 43.28 (4.34) / 0.284 / 0.591
Alkaline Phosphatase / 4.39 (0.48) / 4.35 (0.49) / 0.362 / 0.672
Aspartate Transaminase / 23.32 (11.14) / 23.77 (11.67) / 0.677 / 0.908
Basophils / 1.02 (0.02) / 1.02 (0.02) / 0.337 / 0.652
Bicarbonate - HCO3 / 28.55 (3.61) / 28.87 (3.72) / 0.316 / 0.636
Bilirubin / 11.42 (5.76) / 12.02 (6.32) / 0.279 / 0.588
Caer / 0.32 (0.10) / 0.30 (0.09) / 0.059 / 0.254
Calcium Corrected / 2.29 (0.13) / 2.30 (0.14) / 0.399 / 0.695
Calcium Total / 2.35 (0.14) / 2.37 (0.15) / 0.15 / 0.420
Chloride / 103.27 (4.39) / 103.78 (4.34) / 0.200 / 0.484
Cholestorol / 5.60 (1.68) / 5.51 (1.72) / 0.554 / 0.822
Creatinine / 80.73 (20.79) / 83.45 (21.98) / 0.143 / 0.406
Eosinophils / 0.15 (0.16) / 0.16 (0.17) / 0.826 / 0.951
Erythrocyte Sedimentation Rate / 10.47 (8.65 - 12.77) / 10.32 (7.77 - 13.81) / 0.888 / 0.962
Estimated Glomerular Filtration Rate / 66.98 (17.12) / 65.13 (17.27) / 0.231 / 0.507
Ferritin / 118.04 (109.82 - 127.37) / 126.9(125.73 - 128.03) / 0.479 / 0.772
Free Thyroxine (FT4) / 14.10 (3.08) / 13.25 (2.78) / 0.001 / 0.009
Free Triiodothyronine (FT3) / 4.64 (0.99) / 4.43 (0.96) / 0.015 / 0.085
Gamma-Glutamyl Transferase / 22.17 (17.33) / 21.64 (17.01) / 0.693 / 0.908
Glucose / 5.06 (1.01) / 5.08 (1.04) / 0.855 / 0.951
Hemoglobin / 141.32 (16.47) / 141.24 (16.75) / 0.949 / 0.979
High Density Lipids / 1.64 (0.65) / 1.62 (0.66) / 0.896 / 0.962
Homocysteine / 8.59 (3.90) / 8.97 (4.32) / 0.322 / 0.637
Insulin / 5.61 (5.22 - 6.02) / 6.97 (6.43 - 7.52) / 0.032 / 0.167
Iron / 17.65 (8.15) / 17.81 (8.33) / 0.801 / 0.938
Low Density Lipids / 3.23 (1.52) / 3.17 (1.54) / 0.656 / 0.897
Luteinizing Hormone / 3.57 (1.57) / 3.51 (1.61) / 0.720 / 0.916
Lymphocytes / 1.54 (0.83) / 1.44 (0.78) / 0.153 / 0.423
Mean Corpuscular Haemoglobin Concentration / 342.08 (8.83) / 342.32 (8.99) / 0.702 / 0.908
Mean Corpuscular Hemoglobin / 31.34 (2.56) / 31.12 (2.59) / 0.335 / 0.652
Mean Corpuscular Volume / 91.63 (6.49) / 90.89 (6.57) / 0.201 / 0.484
Mean Platelet Volume / 8.53 (1.49) / 8.64 (1.56) / 0.381 / 0.679
Monocytes / 0.45 (0.22) / 0.43 (0.20) / 0.220 / 0.504
Neutrophils / 3.34 (1.64) / 3.48 (1.73) / 0.361 / 0.672
Oestradiol / 92.41 (85.70) / 83.53 (79.28) / 0.222 / 0.504
Packed Cell Volume / 0.41 (0.05) / 0.41 (0.05) / 0.884 / 0.962
Platelet Count / 241.79 (90.03) / 241.32 (90.85) / 0.928 / 0.973
Potassium / 4.26 (0.48) / 4.22 (0.49) / 0.365 / 0.672
Red Blood Cell Count / 4.51 (0.62) / 4.55 (0.63) / 0.565 / 0.826
Red Blood Cell Distribution Width / 13.40 (1.13) / 13.32 (1.11) / 0.389 / 0.685
Red Cell Folate / 996.71 (583.20) / 956.75 (581.52) / 0.445 / 0.737
Serum Folate / 30.28 (20.22) / 27.83 (19.83) / 0.165 / 0.437
Sodium / 140.57 (3.78) / 141.19 (3.62) / 0.062 / 0.262
Testosterone / 3.31 (2.71 - 4.02) / 3.23 (3.03 - 3.44) / 0.785 / 0.936
Thyroid-Stimulating Hormone / 1.69 (1.53 - 1.85) / 1.87 (1.78 - 1.97) / 0.211 / 0.496
Total Peripheral Resistance / 72.81 (7.54) / 72.99 (7.69) / 0.773 / 0.932
Transferrin / 32.95 (7.02) / 32.94 (7.15) / 0.958 / 0.983
Transferrin Saturation / 27.00 (13.72) / 27.11 (14.01) / 0.903 / 0.964
Triglycerides / 1.14 (0.71) / 1.15 (0.74) / 0.910 / 0.968
Urea / 0.42 (0.08) / 0.41 (0.08) / 0.085 / 0.305
Vitamin B12 / 289.02 (199.68) / 275.52 (190.09) / 0.447 / 0.737
White Blood Cell Count / 5.68 (2.10) / 5.69 (2.14) / 0.958 / 0.983
C: The Metalomics Panel
Analyte / Low NAB [mean (SD) / High NAB [mean (SD) / Raw p / Adj p
Chromium 52 / 2.88 (0.55) / 2.87(0.55) / 0.842 / 0.904
Chromium 53 / 0.54 (0.16) / 0.57 (0.16) / 0.025 / 0.133
Copper 65 / 15.71 (4.30) / 15.11 (4.16) / 0.091 / 0.337
Iron 57 / 21.17 (8.61) / 21.52 (8.79) / 0.656 / 0.820
Rubidium 85 / 2.46 (0.75) / 2.32 (0.72) / 0.023 / 0.131
Selenium 78 / 4.11 (1.26) / 3.99 (1.24) / 0.256 / 0.555
Zinc 66 / 12.04 (2.66) / 11.95 (2.64) / 0.654 / 0.820
E: The Plasma APOE Measurements
Analyte / Low NAB [mean (SD) / High NAB [mean (SD) / Raw p / Adj p
APOE / 14.88 (3.96) / 14.53 (3.97) / 0.307 / N/A
D: The Plasma Aβ Measurements
Analyte / Low NAB [mean (SD) / High NAB [mean (SD) / Raw p / Adj p
Inno Αβ1-40 / 147.89 (56.22) / 147.03 (56.47) / 0.854 / 0.945
Inno Αβ1-42 / 31.67 (16.54) / 30.50 (16.31) / 0.460 / 0.761
Inno Αβ1-40/ Αβ1-42 ratio / 0.23 (0.13) / 0.21 (0.13) / 0.250 / 0.501
Metha Αβ1-40 / 135.76 (96.62) / 121.24 (91.77) / 0.063 / 0.298
Metha Αβ1-42 / 46.06 (24.59) / 42.67 (22.04) / 0.091 / 0.302
Methta Αβ1-40/Αβ1-42 ratio / 0.37 (0.17) / 0.38 (0.18) / 0.514 / 0.787

Supplementary Table 2. Demographic information for A: AIBL Imaged, B: AIBL Non-Imaged and C: ADNI Imaged Datasets split by Clinical Classification. *Interquartile Range (IQR).

A: AIBL Imaged Dataset
HC (169) / MCI (55) / AD (49)
Age [mean (sd)] / 71.7 (7.4) / 75.0 (7.7) / 72.5 (8.9)
Gender: Males [N (%)] / 82 (49) / 28 (51) / 22 (45)
Years of Education [N (%)] / <9: 14 ( 8)
9-12: 64 (38)
13-15: 34 (20)
>15: 57 (34) / <9: 7(13)
9-12: 20 (36)
13-15: 10 (18)
>15: 18 (33) / <9: 7 (14)
9-12: 22 (45)
13-15: 9 (18)
>15: 11 (22)
CDR sum of boxes [median (IQR*)] / 0.0 (0.0 – 0.0) / 0.5 (0.5 – 1.5) / 4.5 (3.5 – 6.0)
APOE e4 positive [N (%)] / 73 (43) / 31 (56) / 34 (69)
B: AIBL Non-Imaged Dataset
HC (584) / MCI (75) / AD (158)
Age [mean (sd)] / 69.6 (6.8) / 76.0 (7.7) / 80.0 (7.8)
Gender: Males [N (%)] / 236 (40) / 28 (37) / 58 (37)
Years of Education [N (%)] / <9: 47 ( 8)
9-12: 219 (38)
13-15: 115 (20)
>15: 200 (34) / <9: 15 (20)
9-12: 33 (45)
13-15: 11 (14)
>15: 15 (20) / <9: 39 (25)
9-12: 51 (34)
13-15: 27 (18)
>15: 35 (23)
CDR sum of boxes [median (IQR*)] / 0.0 (0.0 – 0.0) / 1.0 (0.5 – 2.0) / 5.25 (4.0 – 7.0)
APOE e4positive [N (%)] / 126 (22) / 35 (47) / 95 (60)
C: ADNI Imaged Dataset
HC (3) / MCI (60) / AD (19)
Age [mean (sd)] / 81.3 (5.5) / 79.2 (8.0) / 77.2 (8.7)
Gender: Males [N (%)] / 2 (67) / 18 (30) / 7 (37)
Years of Education [N (%)] / <9: 0 ( 0)
9-12: 1 (33)
13-15: 1 (33)
>15: 1 (33) / <9: 0 ( 0)
9-12: 10 (17)
13-15: 7 (12)
>15: 43 (72) / <9: 0 ( 0)
9-12: 6 (32)
13-15: 4 (21)
>15: 9 (47)
CDR sum of boxes [median (IQR*)] / 0.0 (0.0 – 0.25) / 1.5 (1.0 – 2.0) / 4.5 (3.5 – 5.0)
APOE e4positive [N (%)] / 1 (33) / 31 (52) / 11 (58)

3.SUPPLEMENTARY REFERENCES

1.ADNI Enroll. Demographic Report.

2.ADNI. Biospecimens protocols..

3.ADNI. Biomarkers consortium project: use of targeted multiplex proteomic strategies to identify plasma-based biomarkers in Alzheimer’s Disease.

4.R Development Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria, 2011.

5.van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. Journal of Statistical Software 2011; 45(3): 1-67.

6.Harrell Jr FE. rms: Regression Modeling Strategies. 2012.

7.Fox J, Sandford. An {R} Companion to Applied Regression. Sage2011.

8.Venables WNR, B.D. Modern Applied Statistics with S. Fourth edn. Springer2002.

9.Liaw A, Matthew. Classification and Regression by randomForest. vol. 2. R News2002, pp 18-22.

10.Dimitriadou E, KurtLeisch, FriedrichMeyer, DavidWeingessel, Andreas. e1071: Misc Functions of the Department of Statistic. 2011.

11.Sing T, OliverBeerenwinkel, NikoLengauer, Thomas. ROCR: Visualizing the performance of scoring classifiers. 2009.

12.Wickham H. ggplot2: elegant graphics for data analysis. Springer: New York, 2009.

13.Fox J, Hong J. Effect Displays in R for Multinomial and Proportional-Odds Logit Models: Extensions to the effects Package. Journal of Statistical Software 2009; 32(1): 1-24.