Effects of the monomeric, oligomeric, and fibrillar Aβ₄₂ peptides on the proliferation and differentiation of adult neural stem cells from subventricular zone

The incidence of amyloid plaques, composed mainly of β-amyloid peptides (Aβ), does not correlate well with the severity of neurodegeneration in patients with Alzheimer's disease (AD). The effects of Aβ₄₂ on neurons or neural stem cells (NSCs) in terms of the aggregated form remain controversial. We prepared three forms of oligomeric, fibrillar, and monomeric Aβ₄₂ peptides and investigated their effects on the proliferation and neural differentiation of adult NSCs, according to the degree of aggregation or concentration. A low micromolar concentration (1 μmol/L) of oligomeric Aβ₄₂ increased the proliferation of adult NSCs remarkably in a neurosphere assay. It also enhanced the neuronal differentiation of adult NSCs and their ability to migrate. These results provide us with valuable information regarding the effects of Aβ₄₂ on NSCs in the brains of patients with AD.