PloS one, 2014-01, Vol.9 (1), p.e84547-e84547
2014
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Details
- Autor(en) / Beteiligte
- Titel
- Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitors
- Ist Teil von
- PloS one, 2014-01, Vol.9 (1), p.e84547-e84547
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Presenilin 1 (PSEN1) encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer's disease (FAD). In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs) derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs) from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0084547Titel-ID: cdi_plos_journals_1476178906
- Format
- –
- Schlagworte
- 21st century, Adaptor Proteins, Signal Transducing - genetics, Aging, Alzheimer Disease - pathology, Alzheimer's disease, Amyloid beta-Peptides - biosynthesis, Animals, Apolipoproteins E - genetics, Apoptosis, Apoptosis Regulatory Proteins, B cells, Base Sequence, Biology, Brain - cytology, Brain - pathology, Brain research, Catalysis, Cell Differentiation, Cell Line, Cells (biology), Departments, Eye Proteins - genetics, Fibroblasts, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Genetic aspects, Genomics, Genotype, Humans, Induced Pluripotent Stem Cells - metabolism, Kinases, Medicine, Mutation, Nerve Tissue Proteins - genetics, Neural stem cells, Neural Stem Cells - metabolism, Neurodegenerative diseases, Neurogenesis, Neurology, Neurons, Neurons - cytology, Neurons - pathology, Pathogenesis, Pathology, Peptide Fragments - biosynthesis, Pluripotency, Presenilin 1, Presenilin-1 - genetics, Presenilin-1 - metabolism, Psychiatry, Rats, Secretase, Stem cells, Suppressor of Cytokine Signaling Proteins - genetics, Target marketing