Induced pluripotent stem cells from familial Alzheimer's disease patients differentiate into mature neurons with amyloidogenic properties.
paper
Cited
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- Authors
- Mahairaki, Vasiliki; Ryu, Jiwon; Peters, Ann; Chang, Qing; Li, Tong; Park, Tea Soon; Burridge, Paul W; Talbot, Conover C; Asnaghi, Laura; Martin, Lee J; Zambidis, Elias T; Koliatsos, Vassilis E
- Year
- 2014
- Journal
- Stem cells and development
- PMID
- 25027006
- DOI
- 10.1089/scd.2013.0511
- PMCID
- PMC4267410
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 Ξ²-amyloid (AΞ²)42/AΞ²40 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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