Journal article

Alzheimer risk factors age and female sex induce cortical A beta aggregation by raising extracellular zinc

Zsolt Datki, Zita Galik-Olah, Emese Janosi-Mozes, Viktor Szegedi, Janos Kalman, Akos Gabor Hunya, Livia Fulop, Haruna Tamano, Atsushi Takeda, Paul A Adlard, Ashley Bush

Molecular Psychiatry | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Aging and female sex are the major risk factors for Alzheimer's disease and its associated brain amyloid-β (Aβ) neuropathology, but the mechanisms mediating these risk factors remain uncertain. Evidence indicates that Aβ aggregation by Zn2+ released from glutamatergic neurons contributes to amyloid neuropathology, so we tested whether aging and sex adversely influences this neurophysiology. Using acute hippocampal slices, we found that extracellular Zn2+-elevation induced by high K+ stimulation was significantly greater with older (65 weeks vs 10 weeks old) rats, and was exaggerated in females. This was driven by slower reuptake of extracellular Zn2+, which could be recapitulated by mitochon..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

This project was funded by grants from The National Health and Medical Research Council (GNT1103703, GNT1101533). The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.