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Chunk #4 — INTRODUCTION

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Early pathogenic event of Alzheimer's disease documented in iPSCs from patients with PSEN1 mutations.
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In an attempt to investigate whether there would be alterations in the early stage of neural differentiation from AD-iPSCs, we generated four iPSC lines from fibroblasts of two FAD patients and differentiated them into neural progenitor cells (NPCs). Interestingly, when neuronal differentiation was initiated, these AD-iPSC-derived NPCs (AD-NPCs) displayed premature neuronal differentiation and enhanced apoptosis as well as reduced proliferation, which leads to a decreased NPCs number during differentiation and might be relevant to the neuronal loss of AD. Therefore, this study documents previously unappreciated early neural dysfunctions in NPCs from AD-iPSCs, providing new cues for elucidating early molecular mechanisms underlying AD development.