Effects of Amyloid β-Peptides and Gangliosides on Mouse Neural Stem Cells

The interaction of amyloid beta-proteins (A beta s) with membrane lipids has been postulated as an early event in A beta fibril formation in Alzheimer's disease. We evaluated the effects of several putative bioactive A beta s and gangliosides on neural stem cells (NSCs) isolated from embryonic mouse brains or the subventricular zone of adult mouse brains. Incubation of the isolated NSCs with soluble A beta 1-40 alone did not cause any change in the number of NSCs, but soluble A beta 1-42 increased their number. Aggregated A beta 1-40 and A beta 1-42 increased the number of NSCs but soluble and aggregated A beta 25-35 decreased the number. Soluble A beta 1-40 and A beta 1-42 did not affect the number of apoptotic cells but aggregated A beta 1-40 and A beta 1-42 did. When NSCs were treated with a combination of GM1 or GD3 and soluble A beta 1-42, cell proliferation was enhanced, indicating that both GM1 and GD3 as well as A beta s are involved in promoting cell proliferation and survival of NSCs. These observations suggest the potential of beneficial effects of using gangliosides and A beta s for promoting NSC proliferation.