Title Page

Contents

Abstract 9

Ⅰ. INTRODUCTION 11

Ⅱ. MATERIALS AND METHODS 13

1. Patient derived-iPSC culture 13

2. NPC culture 14

3. Brain cortical neuron differentiation 15

4. Brain cortical neurosphere differentiation 15

5. Drug treatment 16

6. ELISA assay 16

7. Cryosection 17

8. Immunocytochemistry 17

9. Western blot 18

10. Statistical analysis 18

Ⅲ. RESULTS 19

1. Maintenance and characterization of PS1 iPSC colony lines 19

2. NPC induction of PS1 iPSC colony lines 21

3. AD-pathological analysis of PS1 colony line iPSC-derived neurons 21

4. Reduction of Amyloid beta by drug treatment in PS1 colony line iPSC-derived neurons 25

5. Reduction of phosphorylated tau level by drug treatment in PS1 colony line iPSC-derived neurons 29

6. Comparison continuity of MAP2 and GFAP in PS1 colony line iPSC-derived neurons 35

7. PS1 cortical neurosphere induction & differentiation 38

8. Amyloid beta and p-tau expression in PS1 neurosphere 41

9. Control drugs treatment in PS1 neurosphere 41

Ⅳ. DISCUSSION 44

Ⅴ. CONCLUSION 47

REFERENCES 48

ABSTRACT IN KOREAN 51

Figure 1. Characterization of PS1 AD patient-derived colony line iPSCs. 20

Figure 2. Characterization of NPCs from PS1 AD patient-derived colony line iPSCs. 24

Figure 3. Characterization of cortical neurons from PS1 AD patient-derived colony line NPCs. 27

Figure 4. Reduction of Amyloid beta by drug treatment in PS1 colony line iPSC-derived neurons. 28

Figure 5. Reduction of phosphorylated tau level by drug treatment in PS1 colony line iPSC-derived neurons. 32

Figure 6. Immunocytochemistry quantification of the reduction of phosphorylated tau level by drug treatment in PS1 colony line iPSC-derived neurons. 34

Figure 7. Immunocytochemistry quantification of the neurite, and astrocyte level in PS1 colony line iPSC-derived neurons. 37

Figure 8. Protocol of neurosphere induction and differentiation. 38

Figure 9. AD-phenotype expression in PS1 neurosphere. 40

Figure 10. Decrease AD-phenotype expression in PS1 neurosphere. 43