Elevation of serum copper levels in Alzheimer’s disease

Squitti, Rosanna; Lupoi, Domenico; Pasqualetti, Patrizio; Forno, Gloria Dal; Vernieri, Fabrizio; Chiovenda, Paola; Rossi, Luisa; Cortesi, Maurizio; Cassetta, Emanuele; Rossini, Paolo Maria

doi:10.1212/wnl.59.8.1153

Cited by 207 publications

(123 citation statements)

References 60 publications

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“…The enzyme occurs in high intracellular concentrations (10 M in yeast) and has a role in Zn homeostasis and Fe metabolism (40)(41)(42). Two studies (43,44) have shown that a disturbed metal-ion homeostasis with elevated serum Cu levels occurs in AD and Down's patients, and lowered levels in postmortem AD brain (25). A relevant contribution of decreased Cu levels in the brain of AD patients for the formation of A␤ plaques is presently unclear.…”

Section: Discussionmentioning

confidence: 99%

Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice

Bayer

Schäfer

Simons

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

312

255

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The Cu-binding ␤-amyloid precursor protein (APP), and the amyloid A␤ peptide have been proposed to play a role in physiological metal regulation. There is accumulating evidence of an unbalanced Cu homeostasis with a causative or diagnostic link to Alzheimer's disease. Whereas elevated Cu levels are observed in APP knockout mice, APP overexpression results in reduced Cu in transgenic mouse brain. Moreover, Cu induces a decrease in A␤ levels in APP-transfected cells in vitro. To investigate the influence of bioavailable Cu, transgenic APP23 mice received an oral treatment with Cu-supplemented sucrose-sweetened drinking water (1). Chronic APP overexpression per se reduced superoxide dismutase 1 activity in transgenic mouse brain, which could be restored to normal levels after Cu treatment (2). A significant increase of brain Cu indicated its bioavailability on Cu treatment in APP23 mice, whereas Cu levels remained unaffected in littermate controls (3). Cu treatment lowered endogenous CNS A␤ before a detectable reduction of amyloid plaques. Thus, APP23 mice reveal APP-induced alterations linked to Cu homeostasis, which can be reversed by addition of dietary Cu.

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Section: Discussionmentioning

confidence: 99%

Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice

Bayer

Schäfer

Simons

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

312

255

View full text Add to dashboard Cite

show abstract

“…There is new evidence suggesting that brain copper may redistribute outside the neuronal cell, leaving it relatively deficient. 7 Although past studies in man have found no differences between AD and controls in serum copper levels, [8][9][10][11] more sophisticated measurements have recently shown both an increase, [12][13][14][15] and a decrease of these levels, 16,17 thus opening a debate on a toxic or protective role of copper in AD. Results from our laboratory, though, suggest that it is the ceruloplasmin-copper relationship, rather than the level of absolute (i.e., bound and not bound to ceruloplasmin) serum copper, that may be the key issue in interpreting in vivo copper findings in AD.…”

Section: Introductionmentioning

confidence: 99%

Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer disease

Squitti

Quattrocchi

Salustri³

et al. 2008

Prion

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A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We recently demonstrated that an excess of non-ceruloplasmin-copper (i.e., 'free' copper) correlates with the main functional and anatomical deficits as well as the cerebrospinal markers of the disease, thus suggesting that copper contributes to AD neurodegeneration. Aim of this study was to investigate the profile of serum ceruloplasmin isoforms immunoreactive protein in relation to copper dysfunction in AD. Twenty-five AD patients and 25 controls were included in the study. All subjects underwent individual measurements of serum ceruloplasmin and copper concentrations, and the amount of 'free' copper was computed for each copper and ceruloplasmin pair. Serum samples were also pooled and analyzed by two dimensional polyacrylamide gel electrophoresis (2-D PAGE) and western blot analysis. The mean concentration of 'free' copper resulted higher in AD patients than in controls. Ceruloplasmin 2-D PAGE western blot analysis of pooled sera showed in the AD samples low-molecular-weight spots in the <50 kDa range that were not detected in controls' pooled sera (p < 0.029).Our data indicate a ceruloplasmin fragmentation in the serum of AD patients, possibly related to 'free' copper deregulation in this disease.

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“…However, the factors that facilitate Aβ accumulation and how this relates to dementia have remained contentious (2). Various studies have implicated that the toxicity of Aβ is due to abnormal interaction of trace metals zinc, copper and iron in neocortex (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Serum copper in Alzheimer’s disease and vascular dementia

Agarwal

Kushwaha

Tripathi

et al. 2008

Indian J Clin Biochem

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Elevation of serum copper levels in Alzheimer’s disease

Abstract: Copper may play a role in neurodegenerative processes in AD, and serum copper measurement may prove to be a peripheral diagnostic marker for AD.

Cited by 207 publications

References 60 publications

Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice

Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice

Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer disease

Serum copper in Alzheimer’s disease and vascular dementia

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