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• W2085754422 abstract "Redox chemistry arising from transition metals copper and iron are the principal chemical origin of the radicals and reactive oxygen species that are implicated in the pathogenesis of a number of degenerative diseases, such as Alzheimer's disease (AD) (1) and atherosclerosis (2). In health the brain strictly regulates the movement of these metals across the blood–brain barrier (BBB), which is relatively impermeable to fluctuations in blood levels. This barrier is relevant in AD because the disease is characterized by the accumulation in the brain of β-amyloid (Aβ) (3), a copper/zinc-metalloprotein that aggregates and becomes redox-active in the presence of excessive amounts of these metals (4, 5). We are only beginning to unravel the age-dependent failure of metal homeostatic mechanisms of the brain that contribute to abnormal Aβ biochemistry in AD (6).In a recent issue of PNAS, Sparks and Schreurs (7) reported that the ingestion of low concentrations (≈2 μM) of copper in drinking water markedly impairs trace conditioning and increases neuronal and brain parenchymal Aβ immunoreactivity in cholesterol-supplemented rabbits. This finding is provocative because it implies that tap water has sufficient copper contamination to impact the pathophysiology of AD. Although intriguing, there are several caveats before concluding from these data that AD itself is fostered by environmental exposure to copper.The authors report markedly increased Aβ-immunoreactive cortical neurons in the copper-treated rabbits. Cholesterol treatment alone induces an increase, which is significantly augmented by cotreatment with copper. Indeed, tap water treatment alone appears to induce more neuronal Aβ immunoreactivity than distilled water, an effect the authors link to copper contamination. The result suggests that Aβ metabolism is extraordinarily sensitive to small changes in copper concentrations that might be transduced across the BBB. This interpretation is supported by previous observations that both Aβ (5, 8) and the amino …" @default.
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• W2085754422 date "2003-09-23" @default.
• W2085754422 modified "2023-10-12" @default.
• W2085754422 title "Copper, β-amyloid, and Alzheimer's disease: Tapping a sensitive connection" @default.
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• W2085754422 doi "https://doi.org/10.1073/pnas.2135061100" @default.
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