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Neurosci."],"abstract":"<jats:p>Background: Recent studies have indicated that stem cells could provide therapeutic benefits in several neurological conditions, including Alzheimer\u2019s disease (AD). Adipose-derived stem cells (ADSCs) offer many advantages in that they are readily available from individual hosts, are robust, and secrete many factors that promote neuronal growth and homeostasis. Methods: We transfected ADSCs with a viral construct for brain-derived neurotrophic factor (BDNF) and examined the effects of transplanting these cells into the hippocampus of 7-mo-old APPswe\/PS1dE9 mice. After 6 mo, the hippocampus was examined for stem-cell survival, effects on BDNF and neprilysin-2 (NEP-2) levels, dendritic morphology using microtubule associated protein 2 (MAP2) immunohistochemistry, and amyloid plaque load. Results: We found that transplanted BDNF-ADSCs had survived after 6 mo. BDNF and NEP-2 levels were higher than sham controls, and dendritic architecture was improved. In addition, amyloid plaque numbers were reduced. Conclusions: BDNF-ADSCs appear to confer benefits by simultaneously enhancing amyloid clearance and promoting neuronal structural repair. This multifaceted approach highlights the potential of engineering stem cells to target multiple pathophysiological hallmarks of AD, positioning BDNF-ADSCs as a powerful and synergistic cell-gene therapy strategy for this devastating disorder.<\/jats:p>","DOI":"10.31083\/jin46077","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:53:12Z","timestamp":1769687592000},"source":"Crossref","is-referenced-by-count":0,"title":["Adipose-Derived Stem Cells Transfected to Express Brain-Derived Neurotrophic Factor Reduce Hippocampal Amyloid Plaque Load and Improve Dendritic Morphology in the APP\/PS1dE9 Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2509-1576","authenticated-orcid":true,"given":"Yuzhen","family":"Luo","sequence":"first","affiliation":[{"name":"Hainan Province Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment, Hainan Medical University (Hainan Academy of Medical Science), 571199 Haikou, Hainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0248-7287","authenticated-orcid":true,"given":"Yiheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, 571199 Haikou, Hainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6237-8479","authenticated-orcid":true,"given":"Hui","family":"Long","sequence":"additional","affiliation":[{"name":"Hainan Province Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment, Hainan Medical University (Hainan Academy of Medical Science), 571199 Haikou, Hainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6620-1697","authenticated-orcid":true,"given":"Caini","family":"Pei","sequence":"additional","affiliation":[{"name":"Hainan Province Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment, Hainan Medical University (Hainan Academy of Medical Science), 571199 Haikou, Hainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9080-2733","authenticated-orcid":true,"given":"Lujia","family":"Mao","sequence":"additional","affiliation":[{"name":"Hainan Province Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment, Hainan Medical University (Hainan Academy of Medical Science), 571199 Haikou, Hainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-7993","authenticated-orcid":true,"given":"Gregory M.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7126-1781","authenticated-orcid":true,"given":"Haiying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hainan Province Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment, Hainan Medical University (Hainan Academy of Medical Science), 571199 Haikou, Hainan, China"},{"name":"Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, 571199 Haikou, Hainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Lane CA, Hardy J, Schott JM. 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