Measurements of serum non-ceruloplasmin copper by a direct fluorescent method specific to Cu(II)

R. Squitti, M. Siotto, E. Cassetta, I.G. El Idrissi, N.A. Colabufo

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Meta-analyses indicated the breakdown of copper homeostasis in the sporadic form of Alzheimer's disease (AD), comprising copper decreases within the brain and copper increases in the blood and the pool not bound to ceruloplasmin (non-Cp Cu, also known in the literature as "free" copper). The calculated non-Cp Cu (Walshe's) index has many limitations. A direct fluorescent method for non-Cp Cu detection has been developed and data are presented herein. The study included samples from 147 healthy subjects, 36 stable mild cognitive impairment (MCI) and 89 AD patients, who were tested for non-Cp Cu through the direct method, total serum copper, ceruloplasmin concentration and o-dianisidine ceruloplasmin activity. The indirect non-Cp Cu Walshe's index was also calculated. The direct method was linear (0.9-5.9 μM), precise (within-laboratory coefficient variation of 9.7% for low and 7.1% for high measurements), and had a good recovery. A reference interval (0-1.9 μM) was determined parametrically in 147 healthy controls (27-84 years old). The variation of non-Cp Cu was evaluated according to age and sex. Non-Cp Cu was 1.5 times higher in AD patients (regarding the upper value of the reference interval) than in healthy controls. Healthy, MCI and AD subjects were differentiated through the direct non-Cp Cu method [areas under the curve (AUC)=0.755]. Considering a 95% specificity and a 1.91 μmol/L cut-off, the sensitivity was 48.3% (confidence interval 95%: 38%-58%). The likelihood ratio (LR) was 9.94 for positive test results (LR+) and 0.54 for negative test result (LR-). The direct fluorescent test reliably and accurately measures non-Cp Cu, thereby determining the probability of having AD. © 2017 Walter de Gruyter GmbH, Berlin/Boston.
Original languageEnglish
Pages (from-to)1360-1367
Number of pages8
JournalClinical Chemistry and Laboratory Medicine
Volume55
Issue number9
DOIs
Publication statusPublished - 2017

Fingerprint

Copper
Alzheimer Disease
Ceruloplasmin
Serum
Dianisidine
Berlin
Area Under Curve
Meta-Analysis
Brain
Healthy Volunteers
Reference Values
Homeostasis
Blood
Confidence Intervals
Recovery
Cognitive Dysfunction

Keywords

  • Alzheimer's disease
  • ceruloplasmin
  • copper
  • metal
  • mild cognitive impairment
  • non-ceruloplasmin copper
  • cupric ion
  • non ceruloplasmin copper
  • unclassified drug
  • fluorescent dye
  • adult
  • aged
  • Alzheimer disease
  • Article
  • controlled study
  • copper blood level
  • female
  • fluorescence analysis
  • human
  • major clinical study
  • male
  • measurement accuracy
  • priority journal
  • reference value
  • sensitivity and specificity
  • test retest reliability
  • blood
  • chemistry
  • middle aged
  • spectrofluorometry
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Copper
  • Female
  • Fluorescent Dyes
  • Humans
  • Male
  • Middle Aged
  • Spectrometry, Fluorescence

Cite this

Measurements of serum non-ceruloplasmin copper by a direct fluorescent method specific to Cu(II). / Squitti, R.; Siotto, M.; Cassetta, E.; El Idrissi, I.G.; Colabufo, N.A.

In: Clinical Chemistry and Laboratory Medicine, Vol. 55, No. 9, 2017, p. 1360-1367.

Research output: Contribution to journalArticle

Squitti, R. ; Siotto, M. ; Cassetta, E. ; El Idrissi, I.G. ; Colabufo, N.A. / Measurements of serum non-ceruloplasmin copper by a direct fluorescent method specific to Cu(II). In: Clinical Chemistry and Laboratory Medicine. 2017 ; Vol. 55, No. 9. pp. 1360-1367.
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AU - Squitti, R.

AU - Siotto, M.

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AU - El Idrissi, I.G.

AU - Colabufo, N.A.

N1 - Cited By :2 Export Date: 26 February 2018 CODEN: CCLMF Correspondence Address: Squitti, R.; Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Via Pilastroni 4, Italy; email: rsquitti@fatebenefratelli.eu

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N2 - Meta-analyses indicated the breakdown of copper homeostasis in the sporadic form of Alzheimer's disease (AD), comprising copper decreases within the brain and copper increases in the blood and the pool not bound to ceruloplasmin (non-Cp Cu, also known in the literature as "free" copper). The calculated non-Cp Cu (Walshe's) index has many limitations. A direct fluorescent method for non-Cp Cu detection has been developed and data are presented herein. The study included samples from 147 healthy subjects, 36 stable mild cognitive impairment (MCI) and 89 AD patients, who were tested for non-Cp Cu through the direct method, total serum copper, ceruloplasmin concentration and o-dianisidine ceruloplasmin activity. The indirect non-Cp Cu Walshe's index was also calculated. The direct method was linear (0.9-5.9 μM), precise (within-laboratory coefficient variation of 9.7% for low and 7.1% for high measurements), and had a good recovery. A reference interval (0-1.9 μM) was determined parametrically in 147 healthy controls (27-84 years old). The variation of non-Cp Cu was evaluated according to age and sex. Non-Cp Cu was 1.5 times higher in AD patients (regarding the upper value of the reference interval) than in healthy controls. Healthy, MCI and AD subjects were differentiated through the direct non-Cp Cu method [areas under the curve (AUC)=0.755]. Considering a 95% specificity and a 1.91 μmol/L cut-off, the sensitivity was 48.3% (confidence interval 95%: 38%-58%). The likelihood ratio (LR) was 9.94 for positive test results (LR+) and 0.54 for negative test result (LR-). The direct fluorescent test reliably and accurately measures non-Cp Cu, thereby determining the probability of having AD. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

AB - Meta-analyses indicated the breakdown of copper homeostasis in the sporadic form of Alzheimer's disease (AD), comprising copper decreases within the brain and copper increases in the blood and the pool not bound to ceruloplasmin (non-Cp Cu, also known in the literature as "free" copper). The calculated non-Cp Cu (Walshe's) index has many limitations. A direct fluorescent method for non-Cp Cu detection has been developed and data are presented herein. The study included samples from 147 healthy subjects, 36 stable mild cognitive impairment (MCI) and 89 AD patients, who were tested for non-Cp Cu through the direct method, total serum copper, ceruloplasmin concentration and o-dianisidine ceruloplasmin activity. The indirect non-Cp Cu Walshe's index was also calculated. The direct method was linear (0.9-5.9 μM), precise (within-laboratory coefficient variation of 9.7% for low and 7.1% for high measurements), and had a good recovery. A reference interval (0-1.9 μM) was determined parametrically in 147 healthy controls (27-84 years old). The variation of non-Cp Cu was evaluated according to age and sex. Non-Cp Cu was 1.5 times higher in AD patients (regarding the upper value of the reference interval) than in healthy controls. Healthy, MCI and AD subjects were differentiated through the direct non-Cp Cu method [areas under the curve (AUC)=0.755]. Considering a 95% specificity and a 1.91 μmol/L cut-off, the sensitivity was 48.3% (confidence interval 95%: 38%-58%). The likelihood ratio (LR) was 9.94 for positive test results (LR+) and 0.54 for negative test result (LR-). The direct fluorescent test reliably and accurately measures non-Cp Cu, thereby determining the probability of having AD. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

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KW - non ceruloplasmin copper

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KW - adult

KW - aged

KW - Alzheimer disease

KW - Article

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KW - human

KW - major clinical study

KW - male

KW - measurement accuracy

KW - priority journal

KW - reference value

KW - sensitivity and specificity

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KW - blood

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KW - middle aged

KW - spectrofluorometry

KW - very elderly

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Copper

KW - Female

KW - Fluorescent Dyes

KW - Humans

KW - Male

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SN - 1434-6621

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