文献类型：期刊文献

英文题名：AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges

作者：Yu, Zehua[1];Li, Yang[2];Zhang, Zeyu[2];Yin, Rong[1]

第一作者：Yu, Zehua

通信作者：Yin, R[1]

机构：[1]Gansu Prov Cent Hosp, Dept Neurol, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Peoples R China

第一机构：Gansu Prov Cent Hosp, Dept Neurol, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Cent Hosp, Dept Neurol, Lanzhou, Peoples R China.

年份：2026

卷号：18

外文期刊名：FRONTIERS IN AGING NEUROSCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001887653100001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Gansu Provincial Central Hospital (grant numbers GMCCH2025-2-3 and ZDGG-2023-002), the Science and Technology Department of Gansu Province (grant number 26YFFA015), the Health Commission of Gansu Province (grant number GSWSZD2024-06), and the Gansu Stroke Association (grant number GSCZXH-2026-ZD002).

语种：英文

外文关键词：adeno-associated virus; aging; Alzheimer's disease; amyloid-beta; gene therapy; neuroinflammation; tau pathology; translational neuroscience

摘要：Alzheimer's disease remains a major neurodegenerative disorder for which effective disease-modifying treatments are limited. Adeno-associated virus-mediated gene therapy provides a strategy for sustained modulation of disease-related pathways in the central nervous system. Recent studies have explored this approach for regulating amyloid-beta (A beta) metabolism, tau pathology, neuroinflammation, genetic risk factors and neurotrophic support. This review summarizes the biological basis for adeno-associated virus delivery in the central nervous system and discusses major therapeutic strategies for Alzheimer's disease, including approaches targeting A beta production and clearance, tau expression and degradation, immune microenvironment remodeling, apolipoprotein E modulation and synaptic protection. We further examine key translational barriers, including blood-brain barrier restriction, cross-species differences, immune responses, dose-related toxicity, manufacturing constraints and limited clinical evidence. Finally, we propose that future development should move beyond delivery efficiency alone toward biologically informed vector design, target selection, disease-stage matching and biomarker-guided clinical evaluation.