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The role of\n                      <jats:italic>neuronal<\/jats:italic>\n                      microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We utilized in silico analyses of published databases,\n                      <jats:italic>MIR155<\/jats:italic>\n                      \u2010deleted and \u2010overexpressing human induced pluripotent stem cell (hiPSC)\u2010derived cells, cortical organoids, and amyloid beta precursor protein (\n                      <jats:italic>APP<\/jats:italic>\n                      )\n                      <jats:italic>\/PS1\u2010miR155<\/jats:italic>\n                      knockout mouse.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MIR155HG<\/jats:italic>\n                      (miR155 host gene) colocalizes with\n                      <jats:italic>APP<\/jats:italic>\n                      in a neuron\u2010specific, topologically associated domain (TAD) in chromosome 21. In human neural stem cells (NSCs), neurons, and cortical organoids,\n                      <jats:italic>MIR155<\/jats:italic>\n                      deletion enhanced NSC proliferation and GABAergic interneuron generation.\n                      <jats:italic>MIR155<\/jats:italic>\n                      overexpression inhibited NSC marker expression and GABAergic interneuron generation. In\n                      <jats:italic>APP\/PS1<\/jats:italic>\n                      mice,\n                      <jats:italic>miR155<\/jats:italic>\n                      deletion induced the expansion of hippocampal NSCs and increased hippocampal GABAergic interneurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings, alongside the extensive studies of the role of microglial miR155 in neuroinflammation, reveal previously unrecognized miR155 roles in hippocampal NSC dynamics and GABAergic interneuron development, highlighting miR155 as a therapeutic target.<\/jats:p>\n                  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