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Recently, a NeuroD1\u2010mediated neuroregeneration strategy has been proposed, yet its efficacy remains untested in non\u2010human primate (NHP) AD models closely reflecting human pathology. This study evaluates the therapeutic potential of NeuroD1 AAV\u2010based gene therapy in an NHP AD model with hippocampal hTau overexpression, utilizing immunostaining, fluorescence\/confocal imaging, MRI and FDG PET scans, Simoa CSF biomarker analysis, behavioral tests, and bulk RNA sequencing. NeuroD1 AAV\u2010based gene therapy prevents neuronal damage and degeneration, inhibits hippocampal atrophy, and reduces neuroinflammation in NHP AD models. It also repairs vascular and BBB damage, restores CSF AD biomarker levels, improves hippocampal glucose metabolism, and enhances spatial working memory. Transcriptome analysis further reveals upregulated neuronal function and synaptic transmission, along with downregulated neuroinflammation and apoptosis. Collectively, our findings demonstrate that NeuroD1 AAV\u2010based gene therapy repairs and restores brain structure and function in NHP AD models, highlighting its therapeutic potential.<\/jats:p>","DOI":"10.1002\/advs.202520239","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:29:51Z","timestamp":1773156591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A NeuroD1 AAV\u2010Based Gene Therapy for Functional Brain Repair in Alzheimer's Disease\u2010Like Non\u2010Human Primate Model"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhouquan","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules &amp; Druggability Assessment Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules &amp; Discovery of Innovative Drugs Guangdong Key Laboratory of Non\u2010Human Primate Research State Key Laboratory of 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