Sporadic Alzheimer’s Disease in a dish
2019
Harvard Medical School, Boston, USA
The molecular basis of the earliest neuronal changes leading to Alzheimer's disease (AD) is unclear. The aim of this study was to explore the pathogenesis of sporadic Alzheimer's disease (SAD). For this purpose, neural progenitor cells (NPs) generated from iPSCs of SAD patients were compared with those from healthy volunteers and NPs genetically engineered to express APOE4, a common genetic AD risk factor.
These iPSC-derived neural progenitor cells (NPs) and neurons were found to differ in gene networks related to neuronal differentiation, neurogenesis and synaptic transmission. The iPSC-derived neuronal cells from SAD patients showed accelerated neuronal differentiation and reduced progenitor cell renewal. A similar phenotype was also seen in NP cells and cerebral organoids derived from APOE4-iPSCs. It was demonstrated that impaired function of the transcriptional repressor REST is significantly involved in the altered transcriptome and differentiation state. Thus, the dysregulation of neuronal gene networks could set in motion the pathological cascade that leads to Alzheimer's disease.
REST and neural gene network dysregulation in iPSC models of Alzheimer’s disease
Bruce A. Yankner
Added on: 02-24-2022
[1] https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30032-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719300324%3Fshowall%3Dtrue[2] https://www.pcrm.org/news/ethical-science/sporadic-alzheimers-disease-dish-new-cell-model-provides-insights-early
