{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293647/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293647"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Human iPSC-Derived GABAergic Interneuron transplantation rescues circuit dysfunction and tau pathology in Alzheimer’s disease model","description":"Alzheimer's disease (AD) pathophysiology involves disruption of excitatory-inhibitory (E: I) balance and tau accumulation, yet current therapeutic approaches fail to address these interconnected pathologies. Here, we demonstrate that transplanting post-mitotic human iPSC-derived medial ganglionic eminence-originated pallial inhibitory neurons (MGE-pINs) into the hippocampus of 5XFAD mice induces therapeutic effects on synaptic plasticity and cognition through multiple mechanistic pathways. At 6.5 months post transplantation (MPT), MGE-pINs successfully integrated into host neural circuits and restored hippocampal function by attenuating hyperexcitability (72.4% reduction in epileptiform discharges, p<0.001) and normalizing synaptic E: I balance through modulation of GABAA receptor α1/α3 subunit composition and chloride transporter expression. Strikingly, grafts selectively attenuated phosphorylated tau burden by 53-61% (p<0.0001) independent of amyloid-β clearance, while restoring both inhibitory (165.5% increase) and excitatory (65.5% increase) synapse densities (p<0.01). Transcriptomic analysis revealed calcium homeostasis and neuroplasticity pathways, correlating with spatial and working memory performance. Our study establishes a clinically translatable cell therapy that simultaneously targets circuit dysfunction and tau-driven neurodegeneration, providing a paradigm shift for AD intervention.","dates":{"publication":"2026/05/15"},"accession":"GSE293647","cross_references":{"GSM":["GSM8887697","GSM8887698","GSM8887699","GSM8887700","GSM8887701","GSM8887702"],"GPL":["17021"],"GSE":["293647"],"taxon":["Mus musculus"],"PMID":["[42043780]"]}}