Journal article

Extracellular Zn2 Is Essential for Amyloid beta(1-42)-Induced Cognitive Decline in the Normal Brain and Its Rescue

Atsushi Takeda, Haruna Tamano, Munekazu Tempaku, Miku Sasaki, Chihiro Uematsu, Shoko Sato, Hiroaki Kanazawa, Zsolt L Datki, Paul A Adlard, Ashley I Bush

JOURNAL OF NEUROSCIENCE | SOC NEUROSCIENCE | Published : 2017

Abstract

Brain Aβ1-42 accumulation is considered an upstream event in pathogenesis of Alzheimer's disease. However, accumulating evidence indicates that other neurochemical changes potentiate the toxicity of this constitutively generated peptide. Here we report that the interaction of Aβ1-42 with extracellular Zn2+ is essential for in vivo rapid uptake of Aβ1-42 and Zn2+ into dentate granule cells in the normal rat hippocampus. The uptake of both Aβ1-42 and Zn2+ was blocked by CaEDTA, an extracellular Zn2+ chelator, and by Cd2+, a metal that displaces Zn2+ for Aβ1-42 binding. In vivo perforant pathway LTP was unaffected by perfusion with 1000 nm Aβ1-42 in ACSF without Zn2+ However, LTP was attenuated..

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