Journal article

Amyloidogenic processing of Alzheimer's disease beta-amyloid precursor protein induces cellular iron retention

Andrew Tsatsanis, Bruce X Wong, Adam P Gunn, Scott Ayton, Ashley I Bush, David Devos, James A Duce

Molecular Psychiatry | NATURE PUBLISHING GROUP | Published : 2020

Abstract

The proteolytic cleavage of β-amyloid precursor protein (APP) to form the amyloid beta (Aβ) peptide is related to the pathogenesis of Alzheimer's disease (AD) because APP mutations that influence this processing either induce familial AD or mitigate the risk of AD. Yet Aβ formation itself may not be pathogenic. APP promotes neuronal iron efflux by stabilizing the cell-surface presentation of ferroportin, the only iron export channel of cells. Mislocalization of APP can promote iron retention, thus we hypothesized that changes in endocytotic trafficking associated with altered APP processing could contribute to the neuronal iron elevation and oxidative burden that feature in AD pathology. Her..

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Grants

Awarded by Australian National Health & Medical Research Council (NHMRC)


Funding Acknowledgements

We are grateful to Prof. Colin Masters for providing access to the 22C11 antibody and Prof. Nigel Hooper for the fluorescence peptide based on the APP<INF>Swe</INF> sequence (FAM-ISEVNLDAEFR-TAMRA) that was originally gifted to him by GlaxoSmithKline, Stevenage, UK. Flow cytometry was performed by equipment and assistance from the Core Bioimaging facility at Faculty of Biological Sciences, Leeds. Work carried out was supported by Alzheimer's Research UK, the European Research Council and Australian National Health & Medical Research Council (NHMRC) (#1061587).