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The role of metallobiology and amyloid-β peptides in Alzheimer's disease
Abstract
The biggest risk factor for Alzheimer's disease is the process of ageing, but the mechanisms that lead to the manifestation of the disease remain to be elucidated. Why age triggers the disease is unclear but an emerging theme is the inability for a cell to efficiently maintain many key processes such as energy production, repair, and regenerative mechanisms. Metal ions are essential to the metabolic function of every cell. This review will explore the role and reported changes in metal ions in Alzheimer disease, particularly the brain, blood and cerebral spinal fluid, emphasizing how iron, copper and zinc may be involved through the interactions with amyloid precursor protein, the proteolytically cleaved peptide amyloid-beta (Aβ), and other related metalloproteins. Finally, we explore the monomeric makeup of possible Aβ dimers, what a dimeric Aβ species from Alzheimer's disease brain tissue is likely to be composed of, and discuss how metals may influence Aβ production and toxicity via a copper catalyzed dityrosine cross-link.
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“High concentrations of zinc, copper, and iron are present in the insoluble amyloid plaques and neurofibrillary tangles characteristic of Alzheimer’s disease.”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [75]
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“Focal accumulation of zinc, copper, and iron might deprive other brain tissues of these essential metals, leading to aberrant neuronal function.75”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [75]
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Metadata
- Authors
- Roberts, B. R., Ryan, T. M., Bush, A. I., Masters, C. L., & Duce, J. A.
- Affiliations
- Mental Health Research Institute (AU)
- Corresponding author
- Duce, James A.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2011-11-28
- Volume
- 120
- Issue
- s1
- Pages
- 149-166
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1784444703
- Cited by
- 266
- References
- 234
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 18 · 2023: 11 · 2022: 13 · 2021: 17 · 2020: 14 · 2019: 25 · 2018: 16 · 2017: 21 · 2016: 24 · 2015: 22 · 2014: 29 · 2013: 31 · 2012: 19
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- State Government of Victoria
- Australian Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, metal ions, amyloid-beta, amyloid precursor protein, iron, copper, zinc, metalloproteins, amyloid-beta dimers, cerebrospinal fluid, aging, metal homeostasis
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Brain Chemistry, Copper, Humans, Iron, Metalloproteins, Molecular Sequence Data, Protein Binding, Zinc, Amyloid beta-Peptides
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