IMR Press / FBL / Volume 17 / Issue 2 / DOI: 10.2741/3938

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Review
Metals in Alzheimer's disease: a systemic perspective
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1 Department of Neuroscience, AFaR, Fatebenefratelli Hospital, Rome, Italy
2 Department of Neurology, Campus Biomedico, University, Rome, Italy
Front. Biosci. (Landmark Ed) 2012, 17(2), 451–472; https://doi.org/10.2741/3938
Published: 1 January 2012
Abstract

Many results from in vitro and animal studies have highlighted the important role played by specific metals, such as copper, iron and zinc, in the diverse toxic pathways on which Alzheimer's disease (AD) develops. Metals seem to mediate the aggregation and neurotoxicity of amyloid-beta (ABeta), the main constituent of the amyloid plaques, commonly seen in AD (1). The link between metals and AD has been mostly investigated with a focus on their local accumulation in defined areas of the brain critical for AD. In the present review, I have instead approached the issue from the different perspective of a systemic, rather than local, alteration of copper and iron status. This view is supported by the results of a series of in vivo studies demonstrating that abnormalities of metals homeostasis correlate with the main deficits and specific markers of AD, such as ABeta and Tau proteins in the cerebrospinal fluid. These findings clearly suggest that local metals accumulation in brain areas critical for AD should be viewed within a wider framework of metals systemic alteration.

Keywords
Alzheimer’s disease
Metals
Copper
Iron
Oxidative Stress
Antioxidant Status
Ceruloplasmin
Transferrin
Ferritin
Hemochromatosis
HFE
Review
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