文献类型：期刊文献

英文题名：Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer's disease in multiple mouse models

作者：Tang, Siqi[1];Luo, Wenshu[2];Wu, Shihao[3];Yuan, Meng[3];Wen, Jiashuo[3];Zhong, Guoshen[3];Shen, Leshan[4];Jiang, Wei[2,4];Cheng, Cheng[2,4];Wu, Xia[1];Xiao, Xiao[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[2]Belief Biomed Inc, Shanghai 200237, Peoples R China;[3]Yunnan Univ, Sch Med, Kunming 650106, Yunnan, Peoples R China;[4]East China Univ Sci & Technol, Sch Bioengn, Shanghai 200237, Peoples R China

年份：2026

卷号：13

期号：2

外文期刊名：GENES & DISEASES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001643842900001)】；

基金：Funding This work was supported by the National Key Research and Development Program of China (No. 2021YFC2700803) and the National Natural Science Foundation of China (No.82471501, 82360226) .

语种：英文

外文关键词：AAVT42; Alzheime's disease; Brain-derived neurotrophic factor; Cognitive impairment; Hippocampal RNA sequencing

摘要：Brain-derived neurotrophic factor (BDNF) can protect neurons from apoptosis and maintain normal synaptic structures, indicating a significant potential for Alzheimer's disease (AD) treatment. However, the method of in vivo BDNF delivery requires further optimization, and the therapeutic efficacy of BDNF in AD animal models needs to be further evaluated. Here, we demonstrated that a newly engineered adeno-associated virus (AAV) serotype termed AAVT42 showed better tropism for neurons than AAV9 in the central nervous system (CNS). We analyzed the therapeutic potentials of AAVT42-delivered BDNF in three AD mouse models: amyloid precursor protein/presenilin-1 (APP/PS1), rTg4 510, and 3 x Tg. Long-term BDNF expression in the hippocampus mitigated neuronal degeneration or loss in these AD mice, and alleviated their cognitive impairment, with no discernible effect on amyloid-b deposition or tau phosphorylation. Furthermore, transcriptomic analysis in 3 x Tg mice revealed that BDNF orchestrated the up-regulation of genes associated with neuronal structural organization (Bmps). Our study highlighted the efficacy of AAVT42 in gene delivery to CNS and validated the therapeutic benefits of BDNF in treating AD, which will be useful for future translational research on AD treatment using an AAV delivery system.