Neuronal loss is an important pathological feature of AD. Neuronal replacement therapies have already been reported for the treatment of neurodegenerative diseases (Bachoud-Lévi et al., 2006; Mendonça et al., 2015). Neurotransmitters and neuropeptides such as NPY can dynamically regulate adult neurogenesis (Lee et al., 2018). In this regard, Spencer et al. (2016) developed a lentiviral vector expressing NPY, which was fused to a brain transport peptide (apolipoprotein B) for widespread CNS delivery in an amyloid precursor protein-tg mouse model of AD in order to explore the function and role of NPY in neurogenesis of AD (Spencer et al., 2016). The results showed that the proliferation of neural precursor cells in the sub-granular zone of the hippocampus increased significantly without further differentiation into neurons. NPY regulated neurogenesis in the dentate gyrus, caudal subventricular zone (cSVZ), and subcallosal zone via the proliferative effect of Y1 receptors on neuroblasts (Howell et al., 2005; Thiriet et al., 2011). NPY promotes SVZ neurogenesis and increases the number of functional SVZ neurons through the Y1 receptors (Agasse et al., 2008). The neuronal proliferative effect of NPY is mediated by Y1 receptors, and further downstream through a kinase cascade involving protein kinase C and extracellular signal-regulated protein kinases 1 and 2 (Lecat et al., 2015). In the study by Agasse et al. (2008), stress-activated protein kinase/c-Jun N-terminal kinase (P-SAPK/JNK) was found in the cytoplasm and neurite-like structures colocalizing with tau, a microtubule-associated protein mainly present in axons, 6 h after treatment with NPY. Additionally, treatment with NPY increased the total length and number of P-SAPK/JNK-positive ramifications. These data suggest that NPY promotes axonal sprouting and neuronal differentiation through the activation of the SAPK/JNK pathway (Agasse et al., 2008). All the evidence indicate that NPY plays a role in AD by modulating neurogenesis.