Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects

Everett, James; Collingwood, Joanna F.; Tjhin, Vindy Tjendana; Brooks, Jake; Lermyte, Frederik; Plascencia-Villa, Germán; Hands-Portman, Ian; Dobson, Jon; Perry, George; Telling, Neil D.

doi:10.1039/c7nr06794a

Cited by 92 publications

(123 citation statements)

References 84 publications

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“…3), which have been related to dysfunctional iron metabolism [42]. These authors suggest that Aβ is responsible for localised accumulation of redox-active Fe 2+ , through chemical reduction of ferric (Fe 3+ ) iron oxide NPs, and iron in solution at physiological pH in the presence of aggregating Aβ1−42 [33,34]. The ~8-nm magnetite particles these authors observe may reflect conversion of ferrihydrite within the iron-storage protein, ferritin in response to iron overload [25,40].…”

Section: Particulate Air Pollution As An External Source Of Brain Magmentioning

confidence: 93%

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Airborne Magnetite- and Iron-Rich Pollution Nanoparticles: Potential Neurotoxicants and Environmental Risk Factors for Neurodegenerative Disease, Including Alzheimer’s Disease

Maher

2019

JAD

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Fewer than 5% of Alzheimer's disease (AD) cases are demonstrably directly inherited, indicating that environmental factors may be important in initiating and/or promoting the disease. Excess iron is toxic to cells; iron overload in the AD brain may aggressively accelerate AD. Magnetite nanoparticles, capable of catalysing formation of reactive oxygen species, occur in AD plaques and tangles; they are thought to form in situ, from pathological iron dysfunction. A recent study has identified in frontal cortex samples the abundant presence of magnetite nanoparticles consistent with high-temperature formation; identifying therefore their external, not internal source. These magnetite particles range from ~10 to 150 nm in size, and are often associated with other, non-endogenous metals (including platinum, cadmium, cerium). Some display rounded crystal morphologies and fused surface textures, reflecting cooling and crystallization from an initially heated, iron-bearing source material. Precisely-matching magnetite 'nanospheres' occur abundantly in roadside air pollution, arising from vehicle combustion and, especially, frictional brake-wear. Airborne magnetite pollution particles < ~200 nm in size can access the brain directly via the olfactory and/or trigeminal nerves, bypassing the blood-brain barrier. Given their toxicity, abundance in roadside air, and nanoscale dimensions, traffic-derived magnetite pollution nanoparticles may constitute a chronic and pernicious neurotoxicant, and hence an environmental risk factor for AD, for large population numbers globally. Olfactory nerve damage displays strong association with AD development. Reported links between AD and occupational magnetic fields (e.g. affecting welders, machinists) may instead reflect inhalation exposure to airborne magnetic nanoparticles.

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Section: Particulate Air Pollution As An External Source Of Brain Magmentioning

confidence: 93%

“…amyloid plaques) in the brain has been shown to be associated with several different types of neurodegenerative disease, including AD, Parkinson's and Huntington's [27][28][29]32]. A direct correlation between iron accumulation and amyloid plaque pathology has been reported [33][34][35].…”

Section: Iron In the Brain: A Double-edged Swordmentioning

confidence: 99%

Airborne Magnetite- and Iron-Rich Pollution Nanoparticles: Potential Neurotoxicants and Environmental Risk Factors for Neurodegenerative Disease, Including Alzheimer’s Disease

Maher

2019

JAD

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“…However, to date, treatments of neurodegenerative diseases by iron‐chelating agents have not demonstrated compelling clinical effect . The failures may be due to lack of specificity leading to depletion of iron stores and other essential metals required for maintaining neuronal health …”

Section: Strategies To Combat Admentioning

confidence: 99%

Iron and oxidizing species in oxidative stress and Alzheimer's disease

Zhao

2019

Aging Medicine

109

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This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractIron species can participate in the Fenton or Fenton-like reaction to generate oxidizing species that can cause oxidative damages to biomolecules and induce oxidative stress in the body. Furthermore, iron accumulation and oxidative stress have been shown to associate with the pathological progression of neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). In this review, the role of iron species in generating the most deleterious free radical species (ie, hydroxyl radical) and effects of this species in causing oxidative stress in vivo are described. The implications of oxidative stress and the recently recognized cell death pathway (ie, ferroptosis) to AD are addressed. Strategies to combat this neurodegenerative disease, such as iron chelation and antioxidant therapies, and future research directions on this aspect are also discussed. K E Y W O R D SAlzheimer's disease, Fenton/Fenton-like reaction, hydroxyl radical, iron species, oxidative stress | 83 ZHAO treat neurodegenerative diseases. In this review, we examine the role of iron species in generating the most oxidatively deleterious ROS (ie, • OH) and describe the oxidative damages caused by this free radical and its consequence of inducing oxidative stress. We also discuss the association of oxidative stress with AD and the potential therapeutic strategy for this disease.

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“…The amount of iron (Bulk et al, 2018) and ferritin (the major ironbinding protein of the cell; Kwiatek-Majkusiak et al, 2015) in brain tissue is associated with the extent of amyloid deposition. As well as being elevated in neuronal tissue, iron is enriched in the amyloid plaque itself (Meadowcroft, Peters, Dewal, Connor, & Yang, 2014), where the iron is observed to be found in a mineralized magnetite species in humans and mice models (Ayton, James, & Bush, 2017;Everett et al, 2018;Plascencia-Villa et al, 2016;Telling et al, 2017). Magnetite is not a normal feature of brain tissue, so it is likely that this iron species was deposited by an abnormal pathological process.…”

Section: Iron Pathology In Admentioning

confidence: 99%

Treating Alzheimer's disease by targeting iron

Nikseresht

Bush

Ayton

2019

British J Pharmacology

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No disease modifying drugs have been approved for Alzheimer's disease despite recent major investments by industry and governments throughout the world. The burden of Alzheimer's disease is becoming increasingly unsustainable, and given the last decade of clinical trial failures, a renewed understanding of the disease mechanism is called for, and trialling of new therapeutic approaches to slow disease progression is warranted. Here, we review the evidence and rational for targeting brain iron in Alzheimer's disease. Although iron elevation in Alzheimer's disease was reported in the 1950s, renewed interest has been stimulated by the advancement of fluid and imaging biomarkers of brain iron that predict disease progression, and the recent discovery of the iron‐dependent cell death pathway termed ferroptosis. We review these emerging clinical and biochemical findings and propose how this pathway may be targeted therapeutically to slow Alzheimer's disease progression. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects

Abstract: Synchrotron soft X-ray nano-imaging and spectromicroscopy reveals iron and calcium biomineralization in Alzheimer's disease amyloid plaques.

Cited by 92 publications

References 84 publications

Airborne Magnetite- and Iron-Rich Pollution Nanoparticles: Potential Neurotoxicants and Environmental Risk Factors for Neurodegenerative Disease, Including Alzheimer’s Disease

Airborne Magnetite- and Iron-Rich Pollution Nanoparticles: Potential Neurotoxicants and Environmental Risk Factors for Neurodegenerative Disease, Including Alzheimer’s Disease

Iron and oxidizing species in oxidative stress and Alzheimer's disease

Treating Alzheimer's disease by targeting iron

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