Journal
STEM CELLS AND DEVELOPMENT
Volume 23, Issue 24, Pages 2996-3010Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2013.0511
Keywords
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Funding
- Maryland Stem Cell Research Fund [2011-MSCRF-11-0067-00-VEK, 2010-MSCRF-0171-00-VEK, 2011-MSCRF-II-0008-00-ETZ, 2007-MSCRF-II-0379-00-ETZ, 2014-MSCRFE-0724-VM]
- NIH [R01NS045140, 1U01HL099775]
- NIH-NINDS [R01 NS052098, NS079348]
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Although the majority of Alzheimer's disease (AD) cases are sporadic, about 5% of cases are inherited in an autosomal dominant pattern as familial AD (FAD) and manifest at an early age. Mutations in the presenilin 1 (PSEN1) gene account for the majority of early-onset FAD. Here, we describe the generation of virus-free human induced pluripotent stem cells (hiPSCs) derived from fibroblasts of patients harboring the FAD PSEN1 mutation A246E and fibroblasts from healthy age-matched controls using nonintegrating episomal vectors. We have differentiated these hiPSC lines to the neuronal lineage and demonstrated that hiPSC-derived neurons have mature phenotypic and physiological properties. Neurons from mutant hiPSC lines express PSEN1-A246E mutations themselves and show AD-like biochemical features, that is, amyloidogenic processing of amyloid precursor protein (APP) indicated by an increase in beta-amyloid (A beta)42/A beta 40 ratio. FAD hiPSCs harboring disease properties can be used as humanized models to test novel diagnostic methods and therapies and explore novel hypotheses for AD pathogenesis.
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