miR155, triplicated in Down syndrome, regulates the development of neural stem cells and GABAergic interneurons in Alzheimer's disease mouse and human iPSC models.

Authors

• Xiaodong Zhu
• Jean-Vianney Haure-Mirande
• Mesude Bicak
• Pengfei Dong
• Ilya Kruglikov, The Jackson LaboratoryFollow
• Aiqun Li
• Aisha Al-Subaie
• Valentina Fossati, The Jackson LaboratoryFollow
• Scott Noggle
• Sam Gandy
• Michelle E Ehrlich

Document Type

Article

Publication Date

8-1-2026

Original Citation

Zhu X, Haure-Mirande J, Bicak M, Dong P, Kruglikov I, Li A, Al-Subaie A, Fossati V, Noggle S, Gandy S, Ehrlich M. miR155, triplicated in Down syndrome, regulates the development of neural stem cells and GABAergic interneurons in Alzheimer's disease mouse and human iPSC models. Alzheimers Dement. 2026 Aug;22(8):e71684.

Keywords

Animals, MicroRNAs, Humans, Down Syndrome, Alzheimer Disease, Induced Pluripotent Stem Cells, Interneurons, Neural Stem Cells, Disease Models, Animal, Mice, GABAergic Neurons, Amyloid beta-Protein Precursor, Mice, Transgenic, Mice, Knockout

JAX Source

Alzheimers Dement. 2026 Aug;22(8):e71684.

ISSN

1552-5279

PMID

42569825

DOI

https://doi.org/10.1002/alz.71684

Abstract

INTRODUCTION: Dysfunctional microRNAs and GABAergic interneurons are features of Alzheimer's disease (AD). The role of neuronal microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown.

METHODS: We utilized in silico analyses of published databases, MIR155-deleted and -overexpressing human induced pluripotent stem cell (hiPSC)-derived cells, cortical organoids, and amyloid beta precursor protein (APP)/PS1-miR155 knockout mouse.

RESULTS: MIR155HG (miR155 host gene) colocalizes with APP in a neuron-specific, topologically associated domain (TAD) in chromosome 21. In human neural stem cells (NSCs), neurons, and cortical organoids, MIR155 deletion enhanced NSC proliferation and GABAergic interneuron generation. MIR155 overexpression inhibited NSC marker expression and GABAergic interneuron generation. In APP/PS1 mice, miR155 deletion induced the expansion of hippocampal NSCs and increased hippocampal GABAergic interneurons.

DISCUSSION: 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.

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