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To assess the therapeutic potential of stem cell interventions, an AD\u2009+\u2009CCH mouse model was generated by combining APP\/PS1 mice with bilateral common carotid artery stenosis. Neural stem cells (NSCs) or induced pluripotent stem cells (iPSCs) were transplanted into the lateral ventricles at 5\u2009months of age. Behavioral testing, Nissl staining, Western blotting, and immunofluorescence were conducted at 9 and 12\u2009months to evaluate cognition, neuronal survival, cell death pathways (LC3-II, cleaved caspase-3, NLRP3), glial polarization, and neurotrophic\/synaptic markers (BDNF, VEGF, VAChT, PSD95). CCH exacerbated AD-related cognitive deficits, neuronal loss, and activation of autophagic, apoptotic, and pyroptotic pathways, accompanied by enhanced M1 microglial polarization, astrogliosis, and downregulation of BDNF and VAChT. NSCs transplantation significantly improved cognitive performance, preserved neuronal integrity, attenuated glial activation, and restored neurotrophic and synaptic protein expression, characterized by increased BDNF, VEGF, and PSD95 levels and partial recovery of VAChT. In contrast, iPSCs transplantation failed to exert comparable effects. These findings demonstrate that NSCs, but not iPSCs, mitigate AD\u2009+\u2009CCH-induced neuropathology by re-establishing the balance between inflammatory, neurotrophic, and synaptic signaling, supporting NSCs as a promising therapeutic approach for AD with vascular comorbidity.<\/jats:p>","DOI":"10.1177\/0271678x251400239","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T12:20:41Z","timestamp":1765282841000},"page":"1219-1237","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Neural stem cell transplantation attenuates cognitive decline and neuroinflammation in a mouse model of Alzheimer\u2019s disease with chronic cerebral hypoperfusion"],"prefix":"10.1177","volume":"46","author":[{"given":"Zhicheng","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 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