Abstract
A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ1-42 peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at sub-micron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Aβ. We found a direct correlation of amyloid plaque morphology with iron, and evidence for the formation of an iron-amyloid complex. We also show that iron biomineral deposits in the cortical tissue contain the mineral magnetite, and provide evidence that Aβ-induced chemical reduction of iron could occur invivo. Our observations point to the specific role of iron in amyloid deposition and AD pathology, and may impact development of iron-modifying therapeutics for AD.
Highlights
The accumulation of the peptide fragment amyloid-beta (Ab1-42) within the brain is a characteristic hallmark of Alzheimer’s disease (AD) (Selkoe, 1994; Yanker and Lu, 2009)
Studies have suggested that the interaction of metal ions such as iron and aluminum with Ab, and copper and zinc, could play a crucial role in the release of reactive oxygen species (ROS) that contribute to neurodegenerative damage (House et al, 2004; Khan et al, 2006; Smith et al, 1997)
We present the use of X-ray spectromicroscopy in combination with TEM, to determine the oxidation state, magnetic state, and morphology of iron deposits and their relation to pathological features in AD tissue
Summary
Telling et al demonstrate an enhanced role for iron in Alzheimer’s disease pathology, having implications for neurodegeneration, early-stage diagnosis by MRI, and possible treatments based on metal chelation. 2017, Cell Chemical Biology 24, 1205–1215 October 19, 2017 a 2017 The Authors.
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