The Fate and Dynamics of Neural Stem Cells (NSCs) and Their Neurogenic Decline in Alzheimer’s Disease

Neural stem cells (NSCs) are crucial for neurogenesis in the mammalian brain, supporting the generation of neurons and glial cells during both development and adulthood. However, aging—driven by factors such as reduced growth factors, heightened inflammation, oxidative stress, and epigenetic modifications—leads to a decline in NSC activity, which is closely associated with cognitive decline. This article explores the significant reduction in neurogenesis observed in Alzheimer’s disease (AD), where amyloid-beta (Aβ) accumulation, tau pathology, mitochondrial dysfunction, and chronic neuroinflammation disrupt NSC function in the hippocampus and subventricular zone (SVZ). These disruptions impair NSC proliferation, differentiation, and migration, contributing to the progression of cognitive deficits. Additionally, this article examines experimental studies suggesting that deficits in neurogenesis often precede amyloid plaque formation in animal models, positioning impaired neurogenesis as a potential early biomarker for AD. Therapeutic strategies targeting neurogenesis, epigenetics, and inflammation—such as anti-inflammatory treatments, environmental enrichment, and modulation of systemic factors—hold promise for reversing neurogenic deficits and enhancing cognitive function. Furthermore, this article discusses both pharmacological agents and non-pharmacological strategies that show potential in promoting neurogenesis, though further research is needed to evaluate their safety and efficacy. The decline of NSC is driven by many interconnected factors, making it challenging to understand and address fully. This highlights the need for ongoing research.