Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease

Rosanna Squitti, Ilaria Simonelli, Mariacarla Ventriglia, Mariacristina Siotto, Patrizio Pasqualetti, Alan Rembach, James Doecke, Ashley I. Bush

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The fraction of copper not bound to ceruloplasmin seems altered in Alzheimer's disease (AD). We have addressed this notion evaluating all the studies carried out from 1996 until March 2013 by means of meta-analysis. We performed our analysis on diverse indices evaluating the relationship between copper and ceruloplasmin in general circulation, namely 'Non-Cp copper', '% Non-Cp copper', and 'Adjusted copper'. For Non-Cp copper and % Non-Cp copper, the correct stoichiometry between copper and ceruloplasmin (6-8 atoms of copper for each ceruloplasmin molecule) in healthy controls has been adopted as criterion for the study to be included in the meta-analysis evaluating data with the canonic Walshe's formula for Non-Cp copper. Copper to ceruloplasmin ratio (Cu:Cp), which is an internal quality control check for ceruloplasmin calibration, was used as an index of the actual stoichiometry in the specimens. Adjusted (Adj-Cp) copper, even though less reliable, was calculated, allowing the evaluation of all the studies selected. An additional meta-analysis of systemic total copper was re-calculated accounting for all the studies carried out from 1983 to March 2013. Ten studies were analyzed in the meta-analysis for Non-Cp copper and % Non-Cp copper reaching a pooled total of 599 AD subjects and 867 controls. For Adj-Cp copper, 14 studies were analyzed with a pooled total of 879 AD and 1,712 controls. 27 studies were considered for systemic total copper meta-analysis, with a pooled total of 1,393 AD and 2,159 controls. All the copper indices analyzed were significantly higher in AD subjects compared to healthy controls.

Original languageEnglish
Pages (from-to)809-822
Number of pages14
JournalJournal of Alzheimer's Disease
Volume38
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Meta-Analysis
Copper
Alzheimer Disease
Serum
Ceruloplasmin
Quality Control
Calibration

Keywords

  • Alzheimer's disease
  • Ceruloplasmin
  • Copper
  • Metal
  • Plasma
  • Serum

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Squitti, R., Simonelli, I., Ventriglia, M., Siotto, M., Pasqualetti, P., Rembach, A., ... Bush, A. I. (2014). Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease. Journal of Alzheimer's Disease, 38(4), 809-822. https://doi.org/10.3233/JAD-131247

Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease. / Squitti, Rosanna; Simonelli, Ilaria; Ventriglia, Mariacarla; Siotto, Mariacristina; Pasqualetti, Patrizio; Rembach, Alan; Doecke, James; Bush, Ashley I.

In: Journal of Alzheimer's Disease, Vol. 38, No. 4, 2014, p. 809-822.

Research output: Contribution to journalArticle

Squitti, R, Simonelli, I, Ventriglia, M, Siotto, M, Pasqualetti, P, Rembach, A, Doecke, J & Bush, AI 2014, 'Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease', Journal of Alzheimer's Disease, vol. 38, no. 4, pp. 809-822. https://doi.org/10.3233/JAD-131247
Squitti, Rosanna ; Simonelli, Ilaria ; Ventriglia, Mariacarla ; Siotto, Mariacristina ; Pasqualetti, Patrizio ; Rembach, Alan ; Doecke, James ; Bush, Ashley I. / Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease. In: Journal of Alzheimer's Disease. 2014 ; Vol. 38, No. 4. pp. 809-822.
@article{116494748c8e4e7aa228ea47dddd754d,
title = "Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease",
abstract = "The fraction of copper not bound to ceruloplasmin seems altered in Alzheimer's disease (AD). We have addressed this notion evaluating all the studies carried out from 1996 until March 2013 by means of meta-analysis. We performed our analysis on diverse indices evaluating the relationship between copper and ceruloplasmin in general circulation, namely 'Non-Cp copper', '{\%} Non-Cp copper', and 'Adjusted copper'. For Non-Cp copper and {\%} Non-Cp copper, the correct stoichiometry between copper and ceruloplasmin (6-8 atoms of copper for each ceruloplasmin molecule) in healthy controls has been adopted as criterion for the study to be included in the meta-analysis evaluating data with the canonic Walshe's formula for Non-Cp copper. Copper to ceruloplasmin ratio (Cu:Cp), which is an internal quality control check for ceruloplasmin calibration, was used as an index of the actual stoichiometry in the specimens. Adjusted (Adj-Cp) copper, even though less reliable, was calculated, allowing the evaluation of all the studies selected. An additional meta-analysis of systemic total copper was re-calculated accounting for all the studies carried out from 1983 to March 2013. Ten studies were analyzed in the meta-analysis for Non-Cp copper and {\%} Non-Cp copper reaching a pooled total of 599 AD subjects and 867 controls. For Adj-Cp copper, 14 studies were analyzed with a pooled total of 879 AD and 1,712 controls. 27 studies were considered for systemic total copper meta-analysis, with a pooled total of 1,393 AD and 2,159 controls. All the copper indices analyzed were significantly higher in AD subjects compared to healthy controls.",
keywords = "Alzheimer's disease, Ceruloplasmin, Copper, Metal, Plasma, Serum",
author = "Rosanna Squitti and Ilaria Simonelli and Mariacarla Ventriglia and Mariacristina Siotto and Patrizio Pasqualetti and Alan Rembach and James Doecke and Bush, {Ashley I.}",
year = "2014",
doi = "10.3233/JAD-131247",
language = "English",
volume = "38",
pages = "809--822",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "4",

}

TY - JOUR

T1 - Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease

AU - Squitti, Rosanna

AU - Simonelli, Ilaria

AU - Ventriglia, Mariacarla

AU - Siotto, Mariacristina

AU - Pasqualetti, Patrizio

AU - Rembach, Alan

AU - Doecke, James

AU - Bush, Ashley I.

PY - 2014

Y1 - 2014

N2 - The fraction of copper not bound to ceruloplasmin seems altered in Alzheimer's disease (AD). We have addressed this notion evaluating all the studies carried out from 1996 until March 2013 by means of meta-analysis. We performed our analysis on diverse indices evaluating the relationship between copper and ceruloplasmin in general circulation, namely 'Non-Cp copper', '% Non-Cp copper', and 'Adjusted copper'. For Non-Cp copper and % Non-Cp copper, the correct stoichiometry between copper and ceruloplasmin (6-8 atoms of copper for each ceruloplasmin molecule) in healthy controls has been adopted as criterion for the study to be included in the meta-analysis evaluating data with the canonic Walshe's formula for Non-Cp copper. Copper to ceruloplasmin ratio (Cu:Cp), which is an internal quality control check for ceruloplasmin calibration, was used as an index of the actual stoichiometry in the specimens. Adjusted (Adj-Cp) copper, even though less reliable, was calculated, allowing the evaluation of all the studies selected. An additional meta-analysis of systemic total copper was re-calculated accounting for all the studies carried out from 1983 to March 2013. Ten studies were analyzed in the meta-analysis for Non-Cp copper and % Non-Cp copper reaching a pooled total of 599 AD subjects and 867 controls. For Adj-Cp copper, 14 studies were analyzed with a pooled total of 879 AD and 1,712 controls. 27 studies were considered for systemic total copper meta-analysis, with a pooled total of 1,393 AD and 2,159 controls. All the copper indices analyzed were significantly higher in AD subjects compared to healthy controls.

AB - The fraction of copper not bound to ceruloplasmin seems altered in Alzheimer's disease (AD). We have addressed this notion evaluating all the studies carried out from 1996 until March 2013 by means of meta-analysis. We performed our analysis on diverse indices evaluating the relationship between copper and ceruloplasmin in general circulation, namely 'Non-Cp copper', '% Non-Cp copper', and 'Adjusted copper'. For Non-Cp copper and % Non-Cp copper, the correct stoichiometry between copper and ceruloplasmin (6-8 atoms of copper for each ceruloplasmin molecule) in healthy controls has been adopted as criterion for the study to be included in the meta-analysis evaluating data with the canonic Walshe's formula for Non-Cp copper. Copper to ceruloplasmin ratio (Cu:Cp), which is an internal quality control check for ceruloplasmin calibration, was used as an index of the actual stoichiometry in the specimens. Adjusted (Adj-Cp) copper, even though less reliable, was calculated, allowing the evaluation of all the studies selected. An additional meta-analysis of systemic total copper was re-calculated accounting for all the studies carried out from 1983 to March 2013. Ten studies were analyzed in the meta-analysis for Non-Cp copper and % Non-Cp copper reaching a pooled total of 599 AD subjects and 867 controls. For Adj-Cp copper, 14 studies were analyzed with a pooled total of 879 AD and 1,712 controls. 27 studies were considered for systemic total copper meta-analysis, with a pooled total of 1,393 AD and 2,159 controls. All the copper indices analyzed were significantly higher in AD subjects compared to healthy controls.

KW - Alzheimer's disease

KW - Ceruloplasmin

KW - Copper

KW - Metal

KW - Plasma

KW - Serum

UR - http://www.scopus.com/inward/record.url?scp=84890532894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890532894&partnerID=8YFLogxK

U2 - 10.3233/JAD-131247

DO - 10.3233/JAD-131247

M3 - Article

C2 - 24072069

AN - SCOPUS:84890532894

VL - 38

SP - 809

EP - 822

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -