Induced pluripotent stem cells from familial alzheimer's disease patients differentiate into mature neurons with amyloidogenic properties

Vasiliki Machairaki, Jiwon Ryu, Ann Peters, Qing Chang, Tong Li, Tea Soon Park, Paul W. Burridge, Conover C. Talbot, Laura Asnaghi, Lee J Martin, Elias Zambidis, Vassilis El Koliatsos

Research output: Contribution to journalArticle


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 β-Amyloid (Aβ)42/Aβ40 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.

Original languageEnglish (US)
Pages (from-to)2996-3010
Number of pages15
JournalStem Cells and Development
Issue number24
Publication statusPublished - Dec 15 2014


ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

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