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The current study rigorously investigated whether treatment with hiPSC\u2010NSC\u2010EVs could also alleviate several other neuropathological changes contributing to progressive cognitive decline. Three\u2010month\u2010old male and female 5xFAD mice received IN administrations of either hiPSC\u2010NSC\u2010EVs (~30\u2009\u00d7\u200910\n                    <jats:sup>9<\/jats:sup>\n                    \/week for 2\u2009weeks) or vehicle. Two months later, the hippocampus of both male and female 5xFAD mice treated with the vehicle showed increased levels of markers of oxidative stress and mechanistic target of rapamycin (mTOR) signaling, altered expression of genes and\/or proteins linked to mitochondria and autophagy, and diminished neurogenesis. In contrast, treatment with hiPSC\u2010NSC\u2010EVs restored levels of oxidative stress markers and the expression of genes and\/or proteins linked to various mitochondrial complexes, mitochondrial biogenesis, fission, fusion, and mitophagy closer to na\u00efve control levels, indicating alleviation of mitochondrial impairments. These improvements were accompanied by reduced phosphorylated mTOR levels and multiple autophagy markers matching those in na\u00efve controls, suggesting a dampening of mTOR signaling and an enhancement of autophagy. Furthermore, mice treated with hiPSC\u2010NSC\u2010EVs showed increased hippocampal neurogenesis, associated with enhanced brain\u2010derived neurotrophic factor signaling. Overall, the results highlight that IN administrations of hiPSC\u2010NSC\u2010EVs in the early stages of AD can help slow the progression of multiple neuropathological changes associated with cognitive decline in 5xFAD mice and potentially AD.\n                  <\/jats:p>","DOI":"10.1111\/acel.70590","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:31:42Z","timestamp":1781667102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human iPSC\u2010NSC\u2010Derived Extracellular Vesicles Can Alleviate Alzheimer's Disease\u2010Linked Impairments in Mitochondria, mTOR Signaling, Autophagy, and Hippocampal Neurogenesis"],"prefix":"10.1111","volume":"25","author":[{"given":"Leelavathi N.","family":"Madhu","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine, Department of Cell Biology and Genetics Texas A&amp;M University Naresh K Vashisht College of 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