Extracellular Zn2+-independently attenuated LTP by human amyloid β1-40 and rat amyloid β1-42

Abstract Human amyloid-β 1-40 (Aβ 1-40 ) and rat Aβ 1-42 have lower affinity for extracellular Zn 2+ than human Aβ 1-42 . Here we report extracellular Zn 2+ -independent attenuation of dentate gyrus long-term potentiation (LTP) by human Aβ 1-40 and rat Aβ 1-42 . On the basis of the data that dentate gyrus LTP is extracellular Zn 2+ -dependently attenuated after local injection of human Aβ 1-42 (25 pmol, 1 μl) into the dentate gyrus, which increases intracellular Zn 2+ in the dentate gyrus, the toxicity of human Aβ 1-40 and rat Aβ 1-42 was compared in the in vivo system with human Aβ 1-42 . Dentate gyrus LTP was attenuated after injection of human Aβ 1-40 and rat Aβ 1-42 (25 pmol, 1 μl) into the dentate gyrus, which did not increase intracellular Zn 2+ in the dentate gyrus. The attenuated LTP was not rescued by co-injection of CaEDTA, an extracellular Zn 2+ chelator. The present study suggests that human Aβ 1-40 and rat Aβ 1-42 affect cognitive activity via extracellular Zn 2+ -independent mechanism at low micromolar concentration.