Immersion autometallographic tracing of zinc ions in Alzheimer beta-amyloid plaques

Stoltenberg, Meredin; Bruhn, Mikkel; Søndergaard, Claus S.; Doering, P.; West, Mark J.; Larsen, Agnete; Troncoso, Juan C.; Danscher, Gorm

doi:10.1007/s00418-005-0787-0

Cited by 53 publications

(42 citation statements)

References 32 publications

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“…These results were later confirmed by several other research groups (Stoltenberg et al 2005;Miller et al 2006). However, controversial results have been published in an attempt to quantify Zn in AD serum (Rulon et al 2000;Dong et al 2008) or cerebrospinal fluid (CSF) (Molina et al 1998;Gerhardsson et al 2008).…”

Section: Zincsupporting

confidence: 88%

Metal Ion Physiopathology in Neurodegenerative Disorders

2009

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Metal dyshomeostasis in the brain (BMD) has often been proposed as a possible cause for several neurodegenerative disorders (NDs). Nevertheless, the precise nature of the biochemical mechanisms of metal involvement in NDs is still largely unknown. Mounting evidence suggests that normal aging itself is characterized by, among other features, a significant degree of metal ion dysmetabolism in the brain. This is probably the result of a progressive deterioration of the metal regulatory systems and, at least in some cases, of life-long metal exposure and brain accumulation. Although alterations of metal metabolism do occur to some extent in normal aging, they appear to be highly enhanced under various neuropathological conditions, causing increased oxidative stress and favoring abnormal metal-protein interactions. Intriguingly, despite the fact that most common NDs have a distinct etiological basis, they share striking similarities as they are all characterized by a documented brain metal impairment. This review will primarily focus on the alterations of metal homeostasis that are observed in normal aging and in Alzheimer's disease. We also present a brief survey on BMD in other NDs (Amyotrophic Lateral Sclerosis, Parkinson's, and Prion Protein disease) in order to highlight what represents the most reliable evidence supporting a crucial involvement of metals in neurodegeneration. The opportunities for metal-targeted pharmacological strategies in the major NDs are briefly outlined as well.

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Section: Zincsupporting

confidence: 88%

Metal Ion Physiopathology in Neurodegenerative Disorders

2009

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“…But analysis of bulk tissue zinc content is likely to miss the most interesting changes to zinc in the AD brain. In AD, there is a redistribution of zinc into extracellular plaques and surrounding neuropil [71,[79][80][81][82]. Zinc binds Aβ residues 6-28 causing rapid aggregation and precipitation of the peptide [71,83]; thus, co-deposition of zinc with Aβ could initiate plaque formation in the disease.…”

Section: Zincmentioning

confidence: 99%

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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“…These brain slices were then analyzed and photographed with a light microscope. In order to ensure the specificity of the zinc staining, the sodium diethyldithiocarbamate trihydrate (Merck) control procedure was performed as described previously [6,20].…”

Section: Brain Specimens and Tissue Preparationmentioning

confidence: 99%

Immersion autometallographic demonstration of pathological zinc accumulation in human acute neural diseases

et al. 2011

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Zinc is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. In animal experiments, several lines of studies show that zinc is involved in the pathological process of ischemia, epilepsy, and mechanical head trauma. However, little is known about the change of zinc in the human neural diseases. In the present study, using immersion autometallography, we found that pathological zinc accumulation was extensively present in the human neurons following ischemia, epilepsy, and mechanical head trauma. Under H&E, apparently damaged neurons were observed in all of the brain regions that showed zinc ions labeled neuronal somata. In conclusion, the data provide the evidence of an active involvement of zinc in neuronal damage.

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Immersion autometallographic tracing of zinc ions in Alzheimer beta-amyloid plaques

Cited by 53 publications

References 32 publications

Metal Ion Physiopathology in Neurodegenerative Disorders

Metal Ion Physiopathology in Neurodegenerative Disorders

Biometals and Their Therapeutic Implications in Alzheimer's Disease

Immersion autometallographic demonstration of pathological zinc accumulation in human acute neural diseases

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