Hippocampal neural stem cells in Alzheimer’s disease: bridging neurogenesis, extracellular vesicles, and multimodal therapeutic paradigms

Alzheimer's disease (AD) presents a formidable challenge in neurodegenerative medicine because of its complex pathophysiology and the absence of effective disease-modifying therapies. Emerging evidence suggests that impaired adult hippocampal neurogenesis (AHN), a dynamic process essential for cognitive plasticity, is a mechanistic contributor to AD progression. This review highlights the role of hippocampal neural stem cells (NSCs) in the pathogenesis of AD, including the molecular mechanisms underlying the neurogenic decline in AD and their potential impact on cognitive resilience. We summarize current therapeutic approaches, including pharmacological agents and non-pharmacological interventions (e.g. exercise, cognitive training, dietary strategies, and neurostimulation therapies), and explore their influence on neurogenesis. Additionally, we explore the potential application of NSCs in AD treatment, specifically through the use of NSC-derived extracellular vesicles (NSC-EVs) as a novel therapeutic modality. By integrating insights from AHN research and cutting-edge therapeutic advancements, this review emphasizes the therapeutic potential of promoting neurogenesis to address cognitive decline and advance treatment strategies for AD.