Al, Zn, Cu, Mn and Fe levels in brain in Alzheimer's disease

Andrási, Erzsébet; Farkas, É.; Scheibler, Henning; Réffy, A; Bezúr, László

doi:10.1016/0167-4943(95)00643-y

Cited by 94 publications

(48 citation statements)

References 12 publications

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“…Agreement is less pronounced with work of Deibel et al (1996) where no change in zinc concentration was found and iron was reported to increase, rather than decrease. The work of Panayi et al (2002) and Rulon et al (2000) also reported that zinc in the hippocampus was unchanged in averaged AD populations and is at odds with a study from Andrási et al (1995) that reported zinc is reduced by 59%.…”

Section: Literaturementioning

confidence: 78%

Transition metal abnormalities in progressive dementias

et al. 2011

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Abnormal distributions of transition metals inside the brain are potential diagnostic markers for several central nervous system diseases, including Alzheimer's disease (AD), Parkinson's disease, dementia with Lewy bodies (DLB), bipolar disorders and depression. To further explore this possibility, the total concentrations of iron, zinc, copper, manganese, aluminum, chromium and cadmium were measured in post-mortem hippocampus and amygdala tissues taken from AD, DLB and Control patients. A statistically significant near fifty percent reduction in the total copper levels of AD patients was observed in both the hippocampus and amygdala. The statistical power of the hippocampus and amygdala copper analysis was found to be 86 and 74% respectively. No statistically significant deviations in the total metal concentrations were found for zinc, manganese, chromium or aluminum. Iron was found to be increased by 38% in AD amygdala tissues, but was unchanged in AD hippocampus tissues. Accounting for differences in tissue water content, as a function of both tissue type and disease state, revealed more consistencies with previous literature. To aid in the design of future experiments, the effect sizes for all tissue types and metals studied are also presented.

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Section: Literaturementioning

confidence: 78%

Transition metal abnormalities in progressive dementias

et al. 2011

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“…Iron elevation in AD brains, first demonstrated in 1953 [99], is a consistently reported finding [99][100][101][102][103][104][105][106][107][108]. Neuronal iron deposition causes oxidative stress via the Fenton reaction, which might contribute to elevated oxidative stress observed in the AD brain [109].…”

Section: Ironmentioning

confidence: 97%

Biometals and Their Therapeutic Implications in Alzheimer's Disease

2015

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No disease modifying therapy exists for Alzheimer's disease (AD). The growing burden of this disease to our society necessitates continued investment in drug development. Over the last decade, multiple phase 3 clinical trials testing drugs that were designed to target established disease mechanisms of AD have all failed to benefit patients. There is, therefore, a need for new treatment strategies. Changes to the transition metals, zinc, copper, and iron, in AD impact on the molecular mechanisms of disease, and targeting these metals might be an alternative approach to treat the disease. Here we review how metals feature in molecular mechanisms of AD, and we describe preclinical and clinical data that demonstrate the potential for metal-based drug therapy.

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“…The deposition of these metals in the central nervous system increases with age (30), and the distribution changes in neurodegenerative diseases such as Alzheimer's disease (31). Aluminum salts have been shown to modulate the properties of paired helical filaments retarding its degradation by proteases possibly by enhancing aggregation of the protein (22).…”

Section: Reversible Denaturation Of Prp and Infectivity 25546mentioning

confidence: 99%

Reversibility of Scrapie Inactivation Is Enhanced by Copper

McKenzie

Bartz

Mirwald

et al. 1998

Journal of Biological Chemistry

127

101

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The only known difference between the cellular (PrP C ) and scrapie-specific (PrP Sc ) isoforms of the prion protein is conformational. Because disruption of PrP Sc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrP Sc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity. PrP1 is a highly conserved, host-encoded sialoglycoprotein that may play a role in normal synaptic function and circadian rhythms (1, 2). This host protein (PrP C ) is present in the brain and other tissues and is sensitive to proteinase K (PK) digestion (3). During the course of a scrapie infection, PrP C undergoes a post-translational modification to a disease-specific isoform (PrP Sc ) that has increased resistance to limited PK digestion. This modification appears to be solely conformational with PrP Sc having a higher ␤-sheet content than PrP C (4 -7). In vitro cell culture studies have demonstrated that PrP C is the precursor to PrP Sc (8, 9). Inhibition of the migration of PrP C to the cell surface blocks the formation of PrP Sc , confirming that PrP Sc arises via alternate or misprocessing of PrP Sc (8). PrP Sc is resistant to limited PK digestion (10, 11), but upon treatment with GdnHCl, the PrP denatures (12) and becomes sensitive to protease digestion (13). The loss of PK resistance correlates well with loss of infectivity of the PrP Sc -enriched preparation. In this study, we examined the ability of GdnHCl-denatured, PrP Sc -enriched preparations to renature. Renaturation was monitored by Western blot analysis for the presence of PK-resistant PrP and animal bioassay for infectivity. The capacity of PrP to bind copper led us to determine the effect of this transition metal on the renaturation process. EXPERIMENTAL PROCEDURESDenaturation/Renaturation Reactions-Brains were removed from clinically affected hamsters infected with the 263K strain of hamsteradapted scrapie agent, flash frozen, and stored at Ϫ80°C. PrP Sc -enriched fractions were prepared to the P4 pellet step following a modification of Bolton et al. (14) that excludes the PK digestion. The P4 pellet was resuspended in buffered saline containing glycerol (10 mM Tris, pH 7.4, 130 mM NaCl, 5% glycerol), and the protein concentration was determined by the BCA protein assay (Pierce). The reaction conditions for the denaturation and subsequent renaturation were based upon the cell-free conversion reactions described by Kocisko et al. (13). PrP Sc -enriched preparat...

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Al, Zn, Cu, Mn and Fe levels in brain in Alzheimer's disease

Cited by 94 publications

References 12 publications

Transition metal abnormalities in progressive dementias

Transition metal abnormalities in progressive dementias

Biometals and Their Therapeutic Implications in Alzheimer's Disease

Reversibility of Scrapie Inactivation Is Enhanced by Copper

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