Department for Psychiatry, Saarland University, Building 90, 66421 Homburg/Saar, Germany.
Alzheimer's disease (AD) is a devastating brain disorder clinically characterised by progressive loss of characteristic cognitive abilities. Increasing evidence suggests a disturbed copper (Cu) homeostasis to be associated with the pathological processes. In the present study we analysed the plasma Cu levels and cognitive abilities using the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog) in 32 patients with mild to moderate AD. Statistical analysis revealed a negative correlation between plasma Cu levels and cognitive decline (r=-0.49; P<0.01). Patients with low plasma Cu (mean 82 +/- SD 9) had significant higher ADAS-cog values (mean 23 +/- SD 7), than patients with medium plasma Cu (mean 110 +/- SD 7), who exhibited lower ADAS-cog scores (mean 16 +/- SD 4; ANOVA, P<0.0001). Despite the fact that all patients had plasma Cu levels within the physiological range between 65 microg and 165 microg/dL, 87.5% of the patients revealed a significant negative correlation between plasma Cu and ADAS-cog. This finding supports the hypothesis of a mild Cu deficiency in most AD patients.
But there seem to be some studies to the contrary (or maybe those with a deeper understanding of the area can reconcile these results), e.g.,
Results Among persons whose diets were high in saturated and trans fats, higher copper intake was associated with a faster rate of cognitive decline. In multiple-adjusted mixed models, the difference in rates for persons in the highest (median, 2.75 mg/d) vs lowest (median, 0.88 mg/d) quintiles of total copper intake was –6.14 standardized units per year (P<.001) or the equivalent of 19 more years of age. There was also a marginally statistically significant association (P = .07) with the highest quintile of food intake of copper (median, 1.51 mg/d) and a strong dose-response association with higher copper dose in vitamin supplements. Copper intake was not associated with cognitive change among persons whose diets were not high in these fats.
Conclusion These data suggest that high dietary intake of copper in conjunction with a diet high in saturated and trans fats may be associated with accelerated cognitive decline.
One of the articles cited in this article is also available in full text:
Considerable evidence is mounting that dyshomeostasis of the redox-active biometals, Cu and Fe, and oxidative stress contribute to the neuropathology of Alzheimer's disease (AD). Present data suggest that metals can interact directly with Aß peptide, the principal component of ß-amyloid that is one of the primary lesions in AD. The binding of metals to Aß modulates several physiochemical properties of Aß that are thought to be central to the pathogenicity of the peptide. First, we and others have shown that metals can promote the in vitro aggregation into tinctorial Aß amyloid. Studies have confirmed that insoluble amyloid plaques in postmortem AD brain are abnormally enriched in Cu, Fe, and Zn. Conversely, metal chelators dissolve these proteinaceous deposits from postmortem AD brain tissue and attenuate cerebral Aß amyloid burden in APP transgenic mouse models of AD. Second, we have demonstrated that redox-active Cu(II) and, to a lesser extent, Fe(III) are reduced in the presence of Aß with concomitant production of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and hydroxyl radical (OH•). These Aß/metal redox reactions, which are silenced by redox-inert Zn(II), but exacerbated by biological reducing agents, may lead directly to the widespread oxidation damages observed in AD brains. Moreover, studies have also shown that H2O2 mediates Aß cellular toxicity and increases the production of both Aß and amyloid precursor protein (APP). Third, the 5' untranslated region (5'UTR) of APP mRNA has a functional iron-response element (IRE), which is consistent with biochemical evidence that APP is a redox-active metalloprotein. Hence, the redox interactions between Aß, APP, and metals may be at the heart of a pathological positive feedback system wherein Aß amyloidosis and oxidative stress promote each other. The emergence of redox-active metals as key players in AD pathogenesis strongly argues that amyloid-specific metal-complexing agents and antioxidants be investigated as possible disease-modifying agents for treating this horrible disease.
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