Non-Ceruloplasmin Copper Identifies a Subtype of Alzheimer's Disease (CuAD): Characterization of the Cognitive Profile and Case of a CuAD Patient Carrying an

Alzheimer’s disease G-protein Iron RGS7 ceruloplasmin copper dementia dopamine executive functions metals non-bound ceruloplasmin copper stop-loss mutation

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
28 Mar 2023
Historique:
received: 23 02 2023
revised: 22 03 2023
accepted: 25 03 2023
medline: 14 4 2023
entrez: 13 4 2023
pubmed: 14 4 2023
Statut: epublish

Résumé

Alzheimer's disease (AD) is a type of dementia whose cause is incompletely defined. Copper (Cu) involvement in AD etiology was confirmed by a meta-analysis on about 6000 participants, showing that Cu levels were decreased in AD brain specimens, while Cu and non-bound ceruloplasmin Cu (non-Cp Cu) levels were increased in serum/plasma samples. Non-Cp Cu was advocated as a stratification add-on biomarker of a Cu subtype of AD (CuAD subtype). To further circumstantiate this concept, we evaluated non-Cp Cu reliability in classifying subtypes of AD based on the characterization of the cognitive profile. The stratification of the AD patients into normal AD (non-Cp Cu ≤ 1.6 µmol/L) and CuAD (non-Cp Cu > 1.6 µmol/L) showed a significant difference in executive function outcomes, even though patients did not differ in disease duration and severity. Among the Cu-AD patients, a 76-year-old woman showed significantly abnormal levels in the Cu panel and underwent whole exome sequencing. The CuAD patient was detected with possessing the homozygous (c.1486T > C; p.(Ter496Argext*19) stop-loss variant in the

Identifiants

pubmed: 37047347
pii: ijms24076377
doi: 10.3390/ijms24076377
pmc: PMC10094789
pii:
doi:

Substances chimiques

Copper 789U1901C5
Ceruloplasmin EC 1.16.3.1
RGS7 protein, human 0
RGS Proteins 0

Types de publication

Case Reports Meta-Analysis Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Alzheimer's Association
ID : PTC-19-602325
Pays : United States

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Auteurs

Rosanna Squitti (R)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

Claudio Catalli (C)

Osakidetza Basque Health Service, Department of Genetics, Cruces University Hospital, 48903 Barakaldo, Spain.
Neuromuscular Disorders Research Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.

Laura Gigante (L)

Eurofins Genoma Group, Molecular Genetics Laboratory, 00138 Rome, Italy.

Massimo Marianetti (M)

Experimental Alzheimer Center, Fatebenefratelli Roman Province, 00189 Rome, Italy.

Mattia Rosari (M)

Experimental Alzheimer Center, Fatebenefratelli Roman Province, 00189 Rome, Italy.

Stefania Mariani (S)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

Serena Bucossi (S)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

Gioia Mastromoro (G)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

Mariacarla Ventriglia (M)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

Ilaria Simonelli (I)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

Vincenzo Tondolo (V)

Digestive and Colorectal Surgery, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.
Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Parminder Singh (P)

Centre for Systems Biology and Bioinformatics, Panjab University, Chandigarh 160025, India.

Ashok Kumar (A)

Centre for Systems Biology and Bioinformatics, Panjab University, Chandigarh 160025, India.

Amit Pal (A)

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Kalyani 741245, India.

Mauro Rongioletti (M)

Department of Laboratory Science, Research and Development Division, Fatebenefratelli Isola Tiberina-Gemelli Isola, 00186 Rome, Italy.

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Classifications MeSH