Supplementary Materials for: Cellular phenotyping of hippocampal progenitors exposed to patient serum predicts conversion to Alzheimer’s Disease Aleksandra Maruszak, Tytus Murphy, Benjamine Liu, Chiara de Lucia, Abdel Douiri, Alejo J Nevado, Charlotte E Teunissen, Pieter Jelle Visser, Jack Price, Simon Lovestone, Sandrine Thuret* *Corresponding author: [email protected] This file includes: Fig. S1. Receiver-operator characteristic-curve for the cross-validation model predicting conversion to Alzheimer’s disease. Fig. S2. Receiver-operator characteristic-curve for predicting conversion to Alzheimer’s disease using a panel of 207 proteins. Table S1. Comparison of AUC for logistic regression models for individual predictors. Table S2. 207 proteins significantly differentially expressed between MCI converters and non- converters. 1 Fig. S1. Receiver-operator characteristic-curve for the cross-validation model predicting conversion to Alzheimer’s disease. Area under the curve, AUC=0.93, Sensitivity 90.3%, Specificity 79.0%. 2 Fig. S2. Receiver-operator characteristic-curve for predicting conversion to Alzheimer’s disease using a panel of 207 proteins. Area under the curve, AUC=0.943 Sensitivity= 91.65%, Specificity= 81.68%. 3 Table S3. Comparison of AUC for logistic regression models for individual predictors. P- value refers to the model. AUC OR SE 95% CI R2 p Education (years) 0.7562 0.79 0.06 0.68-0.93 0.1433 0.001 Average cell count 0.8080 1.01 0.004 1.01-1.024 0.3069 <0.0001 (proliferation) %Ki67+ cells (proliferation) 0.5728 1.04 0.05 0.94-1.15 0.0104 0.3919 %CC3+ cells (differentiation) 0.7972 2.97 1.08 1.45-6.08 0.2154 0.0001 4 Table S4. 207 proteins significantly differentially expressed between MCI converters and non-converters. No Bonferroni correction was applied. Protein Name Protein UniProt EntrezGeneSymbol p-value Fold Symbol change (log10) Gro-beta/gamma Gro-b/g P19876, CXCL3, CXCL2 0.0004 -0.028 P19875 Solute carrier family S35G2 Q8TBE7 SLC35G2 0.0005 0.016 35 member G2 Interferon-induced CIG49 O14879 IFIT3 0.0006 -0.022 protein with tetratricopeptide repeats 3 C-C motif chemokine MDC O00626 CCL22 0.0014 -0.023 22 Protein quaking QKI Q96PU8 QKI 0.0017 -0.034 CREB-binding CREB- Q92793 CREBBP 0.0017 0.009 protein binding protein Patched domain- PTHD3 Q3KNS1 PTCHD3 0.0018 -0.011 containing protein 3 Semaphorin-4D SEM4D Q92854 SEMA4D 0.0020 0.018 5 Inactive dipeptidyl DPP10 Q8N608 DPP10 0.0028 -0.010 peptidase 10 Profilin-2 Profilin II P35080 PFN2 0.0040 0.010 Connective tissue- CTAP-III P02775 PPBP 0.0041 -0.008 activating peptide III Neuralized-like NEUL4 Q96JN8 NEURL4 0.0042 0.014 protein 4 AH receptor- AIP O00170 AIP 0.0049 0.012 interacting protein Carbonic anhydrase 2 carbonic P00918 CA2 0.0053 -0.030 anhydrase II MIP18 family protein FA96A Q9H5X1 FAM96A 0.0057 -0.022 FAM96A Ribosome-binding RRBP1 Q9P2E9 RRBP1 0.0058 -0.022 protein 1 COP9 signalosome CSN2 P61201 COPS2 0.0059 0.014 complex subunit 2 Immunoglobulin IGDC3 Q8IVU1 IGDCC3 0.0064 -0.011 superfamily DCC subclass member 3 Secreted frizzled- SARP-2 Q8N474 SFRP1 0.0067 0.055 related protein 1 6 Malonyl-CoA DCMC O95822 MLYCD 0.0067 -0.012 decarboxylase, mitochondrial Dickkopf-related DKK1 O94907 DKK1 0.0068 -0.020 protein 1 Interferon lambda-3 IFN- Q8IZI9 IFNL3 0.0075 -0.020 lambda 3 Translationally- TCTP P13693 TPT1 0.0076 0.007 controlled tumor protein Platelet-derived PDGF-AA P04085 PDGFA 0.0080 -0.014 growth factor subunit A Semaphorin-3A Semaphorin Q14563 SEMA3A 0.0080 0.011 3A Ubiquitin carboxyl- UBP21 Q9UK80 USP21 0.0081 0.010 terminal hydrolase 21 Plasminogen activator PAI-1 P05121 SERPINE1 0.0081 -0.020 inhibitor 1 Neuropilin and NETO2 Q8NC67 NETO2 0.0084 0.012 tolloid-like protein 2 Oxysterols receptor NR1H2 P55055 NR1H2 0.0088 0.008 LXR-beta 7 Vasorin VASN Q6EMK4 VASN 0.0090 0.008 Glycoprotein Xg XG P55808 XG 0.0093 0.010 NKG2D ligand 1 ULBP-1 Q9BZM6 ULBP1 0.0094 -0.019 Basic leucine zipper BATF3 Q9NR55 BATF3 0.0096 -0.006 transcriptional factor ATF-like 3 Protein transport SC61B P60468 SEC61B 0.0098 -0.015 protein Sec61 subunit beta Integral membrane ITM2A O43736 ITM2A 0.0100 0.009 protein 2A FAS-associated factor FAF2 Q96CS3 FAF2 0.0102 -0.013 2 Dickkopf-related Dkk-4 Q9UBT3 DKK4 0.0102 -0.020 protein 4 NACHT, LRR and NALP4 Q96MN2 NLRP4 0.0105 -0.008 PYD domains- containing protein 4 C-C motif chemokine TARC Q92583 CCL17 0.0108 -0.031 17 Progonadoliberin-1 GON1 P01148 GNRH1 0.0111 0.010 Platelet factor 4 PF-4 P02776 PF4 0.0115 -0.005 8 Transmembrane CP054 Q6UWD8 C16orf54 0.0119 -0.055 protein C16orf54 Biotinidase Biotinidase P43251 BTD 0.0121 0.022 Uncharacterized CA115 Q9H7X2 C1orf115 0.0123 -0.006 protein C1orf115 C-X-C motif ENA-78 P42830 CXCL5 0.0131 -0.011 chemokine 5 Interleukin-36 alpha IL-1F6 Q9UHA7 IL36A 0.0132 0.040 GTP-binding protein GEM P55040 GEM 0.0134 0.021 GEM Glycerol-3-phosphate GPDA P21695 GPD1 0.0134 0.034 dehydrogenase [NAD(+)], cytoplasmic Interleukin-1 IL-1 R AcP Q9NPH3 IL1RAP 0.0134 0.028 Receptor accessory protein Tumor necrosis factor BAFF Q96RJ3 TNFRSF13C 0.0136 0.028 receptor superfamily Receptor member 13C Probable DIM1 Q9UNQ2 DIMT1 0.0139 -0.022 dimethyladenosine transferase 9 Fermitin family URP2 Q86UX7 FERMT3 0.0141 -0.028 homolog 3 Histidine triad HINT2 Q9BX68 HINT2 0.0142 0.012 nucleotide-binding protein 2, mitochondrial 2-phosphoxylose ACPL2 Q8TE99 ACPL2 0.0142 0.009 phosphatase 1 Glutamate receptor 4 GRIA4 P48058 GRIA4 0.0146 0.010 Mesencephalic ARMET P55145 MANF 0.0146 -0.028 astrocyte-derived neurotrophic factor Carbohydrate CHST3 Q7LGC8 CHST3 0.0148 -0.009 sulfotransferase 3 C1GALT1-specific C1GLC Q96EU7 C1GALT1C1 0.0151 0.009 chaperone 1 ETS domain- ELK1 P19419 ELK1 0.0151 0.007 containing protein Elk-1 Prolactin-releasing PRRP P81277 PRLH 0.0152 0.010 peptide Calpain-2 catalytic CAN2 P17655 CAPN2 0.0154 -0.014 subunit 10 Amphoterin-induced AMGO1 Q86WK6 AMIGO1 0.0158 -0.058 protein 1 Acid-sensing ion ASIC4 Q96FT7 ASIC4 0.0159 0.007 channel 4 72 kDa inositol INP5E Q9NRR6 INPP5E 0.0161 -0.005 polyphosphate 5- phosphatase A disintegrin and ATS3 O15072 ADAMTS3 0.0164 0.006 metalloproteinase with thrombospondin motifs 3 Protein eva-1 F176C P58658 EVA1C 0.0166 0.012 homolog C Lysosome membrane LIMP II Q14108 SCARB2 0.0167 -0.010 protein 2 Calcium/calmodulin- CAMK1 Q14012 CAMK1 0.0179 0.006 dependent protein kinase type 1 Retinaldehyde- RLBP1 P12271 RLBP1 0.0181 0.010 binding protein 1 Protein lin-7 homolog LIN7B Q9HAP6 LIN7B 0.0182 -0.006 B 11 DNA primase small PRI1 P49642 PRIM1 0.0183 -0.011 subunit T-cell surface CD3E P07766 CD3E 0.0184 0.010 glycoprotein CD3 epsilon chain C-type lectin domain CLC2L P0C7M8 CLEC2L 0.0186 -0.009 family 2 member L Protein SERAC1 SRAC1 Q96JX3 SERAC1 0.0186 0.011 Arylamine N- ARY1 P18440 NAT1 0.0188 0.010 acetyltransferase 1 Fibrinogen C domain- FBCD1 Q8N539 FIBCD1 0.0191 0.007 containing protein 1 Microtubule- MLP3B Q9GZQ8 MAP1LC3B 0.0191 -0.011 associated proteins 1A/1B light chain 3B Persulfide ETHE1 O95571 ETHE1 0.0191 0.012 dioxygenase ETHE1, mitochondrial Ferritin, FTMT Q8N4E7 FTMT 0.0194 0.026 mitochondrial Sulfhydryl oxidase 1 QSCN6 O00391 QSOX1 0.0203 0.008 Kinesin light chain 1 KLC1 Q07866 KLC1 0.0203 0.011 Protein FAM171A2 F1712 A8MVW0 FAM171A2 0.0203 0.011 12 Syntaxin-6 Syntaxin-6 O43752 STX6 0.0204 -0.004 Cytohesin-interacting CYTIP O60759 CYTIP 0.0207 -0.016 protein SPARC-related SMOC1 Q9H4F8 SMOC1 0.0208 0.007 modular calcium- binding protein 1 Leucine-rich repeat, LRIT3 Q3SXY7 LRIT3 0.0211 -0.010 immunoglobulin-like domain and transmembrane domain-containing protein 3 Protein Z-dependent protein Z Q9UK55 SERPINA10 0.0214 0.019 protease inhibitor inhibitor Fatty acid-binding FABPE Q01469 FABP5 0.0218 0.009 protein, epidermal TYMS opposite CR056 Q8TAI1 TYMSOS 0.0221 0.011 strand protein Microtubule- tau P10636 MAPT 0.0222 -0.014 associated protein tau Dedicator of DOCK9 Q9BZ29 DOCK9 0.0223 0.005 cytokinesis protein 9 13 Tumor necrosis factor RELT Q969Z4 RELT 0.0223 0.007 receptor superfamily member 19L Apolipoprotein A-V Apo A-V Q6Q788 APOA5 0.0225 0.018 Tumor necrosis factor TRAIL R1 O00220 TNFRSF10A 0.0226 0.010 receptor superfamily member 10A Caseinolytic peptidase CLPB Q9H078 CLPB 0.0227 0.020 B protein homolog Collagen alpha-1(XX) COKA1 Q9P218 COL20A1 0.0232 -0.041 chain Insulin-like peptide INSL5 Q9Y5Q6 INSL5 0.0232 0.022 INSL5 Glial fibrillary acidic GFAP P14136 GFAP 0.0233 -0.017 protein Zinc fingers and ZHX1 Q9UKY1 ZHX1 0.0233 -0.019 homeoboxes protein 1 Platelet-derived PDGF-BB P01127 PDGFB 0.0236 -0.014 growth factor subunit B Peptidase inhibitor 15 PI15 O43692 PI15 0.0237 0.008 Regulator of G- RGS7 P49802 RGS7 0.0246 0.017 protein signaling 7 14 Colipase-like protein CF126 Q6UWE3 CLPSL2 0.0248 0.009 2 Epididymal secretory EP3B P56851 EDDM3B 0.0254 -0.006 protein E3-beta DnaJ homolog DJC17 Q9NVM6 DNAJC17 0.0259 0.010 subfamily C member 17 SAGA-associated SGF29 Q96ES7 CCDC101 0.0259 -0.008 factor 29 homolog Trem-like transcript 1 TRML1 Q86YW5 TREML1 0.0260 -0.019 protein Peptidyl-glycine AMD P19021 PAM 0.0260 0.017 alpha-amidating monooxygenase E3 ubiquitin-protein RNF8 O76064 RNF8 0.0268 0.009 ligase RNF8 Selenoprotein S SELS Q9BQE4 VIMP 0.0269 0.010 Protein FAM107B FAM107B Q9H098 FAM107B 0.0275 0.006 WSC domain- WSCD2 Q2TBF2 WSCD2 0.0277 0.008 containing protein 2 Alpha-enolase Alpha P06733 ENO1 0.0277 0.019 enolase 15 Hemoglobin subunit HBAZ P02008 HBZ 0.0277 0.009 zeta Interferon-induced IFIT2 P09913 IFIT2 0.0280 0.012 protein with tetratricopeptide repeats 2 Leucine-rich repeats LRIG3 Q6UXM1 LRIG3 0.0280 0.013 and immunoglobulin- like