The Role of iPSC Research at the Shiley Marcos ADRC Lawrence - PowerPoint PPT Presentation

The Role of iPSC Research at the Shiley Marcos ADRC Lawrence Goldstein, PhD 1

ALZHEIMER’S DISEASE (AD)  AD IS COMMON, PROGRESSIVE, AND INCURABLE  ONLY A FEW TREATMENTS KNOWN-HAVE MINIMAL EFFECT  SYNAPSE LOSS  EVENTUAL MASSIVE NEURONAL DEATH TANGLES PLAQUES THE AMYLOID CASCADE HYPOTHESIS FROM FROM WWW- www.northwestern.edu/nuin/facult MEDLIB.MED.UTAH.EDU/WEBPATH/WEB y/Binder_L/ PATH.HTML TRANSMEMBRANE BETA-SECRETASE APP (BACE) A β EXTRACELLULAR DOMAIN GAMMA-SECRETASE (PRESENILIN) CYTOPLASMIC 2

AD PHENOTYPES IN FAD AND SAD HIPSC DERIVED NEURONS ISRAEL ET AL., NATURE 2012 A β GSK3 PHOSPHO- PEPTIDE? KINASE? TAU? 3 NDC SAD FAD NDC SAD FAD NDC SAD FAD

WHAT IS UPSTREAM OF P-TAU? VAN DER KANT AND LANGNESS CELL STEM CELL 2019 4

ARE ALL PATIENT LINES AFFECTED? VAN DER KANT AND LANGNESS CELL STEM CELL 2019 5

DOES P-TAU DEPEND ON ABETA? VAN DER KANT AND LANGNESS CELL STEM CELL 2019 6

WHAT ARE LIKELY MECHANISTIC CONCLUSIONS? VAN DER KANT AND LANGNESS CELL STEM CELL 2019 7

APPROVED DRUGS THAT ALTER CHOLESTERYL-ESTER SUPPRESS NFT PHENOTYPE 8

THANK YOU!! CHOLESTEROL AND P-TAU HUMAN MODELS OF AD CHERYL HERRERA MASON ISRAEL-UCSD DAN WILLIAMS SHAUNA YUAN-UCSD STEVE WAGNER GRACE WOODRUFF-UCSD ANNE BANG SOL REYNA-UCSD VANESSA LANGNESS CHERYL HERRERA-UCSD RIK VAN DER KANT JESSICA YOUNG-UCSD CEDRIC BARDY-SALK AD COLLABORATORS YANGLING MU-SALK BEN YU & UCSD ADRC (SKIN BIOPSIES) FRED GAGE-SALK ANNE REMES (FINNISH FIBROBLASTS) EDDIE KOO FUNDING STEVE DOWDY LAB (REPROGRAMMING VECTORS) CIRM ADRC BIOPSY NIH PARTICIPANTS! 9 9