<p>Neurogenesis is a biological process in which new neurons are generated from neural stem cells (NSCs) in specific neural niches in the brain. Impaired neurogenesis, characterized by the progressive loss of neurons, leads to cognitive and motor disabilities and is a hallmark of central nervous system (CNS) diseases. Conversely, enhancing neurogenesis has been shown to alleviate the symptoms of CNS diseases. Apolipoprotein E (APOE) is a protein that plays various biological roles in CNS diseases. Emerging research indicates that APOE is involved in adult neurogenesis, which is crucial for maintaining the neural progenitor pool in the dentate gyrus (DG) and synaptic activity. Therefore, APOE could be a therapeutic target for promoting neurogenesis in the treatment and intervention of CNS diseases. In this context, we present a comprehensive overview of the clinical evidence supporting the role of APOE in CNS diseases on the basis of a meta-analysis. We also discuss the neurogenic potential of APOE, which has significant implications not only for understanding the biological underpinnings of neurological diseases but also for developing novel treatment strategies for CNS diseases.</p>