Neurogenesis Is Increased in Human Neural Stem Cells by Aβ40 Peptide

Amyloid-beta 40 peptides [A beta 1-40 (A beta 40)] are present within amyloid plaques in the brains of patients with Alzheimer's disease (AD). Even though A beta peptides are considered neurotoxic, they can mediate many biological processes, both in adult brains and throughout brain development. However, the physiological function of these A beta peptides remains poorly understood, and the existing data are sometimes controversial. Here, we analyze and compare the effects of monomeric A beta 40 on the biology of differentiating human neural stem cells (human NSCs). For that purpose, we used a model of human NSCs called hNS1. Our data demonstrated that A beta 40 at high concentrations provokes apoptotic cellular death and the damage of DNA in human NSCs while also increasing the proliferation and favors neurogenesis by raising the percentage of proliferating neuronal precursors. These effects can be mediated, at least in part, by beta-catenin. These results provide evidence of how A beta modulate/regulate human NSC proliferation and differentiation, suggesting A beta 40 may be a pro-neurogenic factor. Our data could contribute to a better understanding of the molecular mechanisms involved in AD pathology and to the development of human NSC-based therapies for AD treatment, since these results could then be used in diagnosing the disease at early stages and be applied to the development of new treatment options.