ArticleMolecular neurobiology2017
Non-Ceruloplasmin Copper Distincts Subtypes in Alzheimer's Disease: a Genetic Study of ATP7B Frequency.
Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Copper Imbalance in Alzheimer's Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study EvaluatingBiomolecules · 2021Pooled it
- CLSI Validation of Exchangeable Copper Determination in Serum by ICP-MS: A Focus on Alzheimer's Disease and Wilson Disease.Biomolecules · 2025Article
- Ramp Sequence May Explain Synonymous Variant Association with Alzheimer's Disease in the Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRA).Biomedicines · 2025Article
- Downregulation of Parahippocampal Copper Chaperone for Superoxide Dismutase in Alzheimer's Disease.Brain sciences · 2025Article
- Ramp sequence may explain synonymous variant association with Alzheimer's disease in the Paired Immunoglobulin-like Type 2 Receptor Alpha (bioRxiv : the preprint server for biology · 2025Article
- The Role of Copper in Alzheimer's Disease Etiopathogenesis: An Updated Systematic Review.Toxics · 2024Review
- Design and Development of Inexpensive Paper-Based Chemosensors for Detection of Divalent Copper.Journal of fluorescence · 2023Article
- A fluorometric assay to determine labile copper(II) ions in serum.Scientific reports · 2023Article
- Secretion and uptake of copper via a small copper carrier in blood fluid.Metallomics : integrated biometal science · 2022Article
- Microglia and Astrocytes in Alzheimer's Disease in the Context of the Aberrant Copper Homeostasis Hypothesis.Biomolecules · 2021Review
- Nerve Growth Factor Peptides Bind Copper(II) with High Affinity: A Thermodynamic Approach to Unveil Overlooked Neurotrophin Roles.International journal of molecular sciences · 2021Article
- Apoceruloplasmin: Abundance, Detection, Formation, and Metabolism.Biomedicines · 2021Review
- Copper Toxicity Links to Pathogenesis of Alzheimer's Disease and Therapeutics Approaches.International journal of molecular sciences · 2020Review
- Agricultural Use of Copper and Its Link to Alzheimer's Disease.Biomolecules · 2020Review
- Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques.Metallomics : integrated biometal science · 2020Article
- A case of a mild Wolfram Syndrome with concomitantCellR4-- repair, replacement, regeneration, & reprogramming · 2019Article
- Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.Antioxidants & redox signaling · 2018Review
- Commentary: The Case for Abandoning Therapeutic Chelation of Copper Ions in Alzheimer's Disease.Frontiers in neurology · 2017Article
- Role of Copper in the Onset of Alzheimer's Disease Compared to Other Metals.Frontiers in aging neuroscience · 2017Review
- Diabetes and Alzheimer's Disease: Can Elevated Free Copper Predict the Risk of the Disease?Journal of Alzheimer's disease : JAD · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Meta-analyses show that serum copper non-bound-to-ceruloplasmin (non-Cp-Cu) is higher in patients with Alzheimer's disease (AD). ATP7B gene variants associate with AD, modulating the size of non-Cp-Cu pool. However, a dedicated genetic study comparing AD patients after stratification for a copper biomarker to demonstrate the existence of a copper subtype of AD has not yet been carried out. An independent patient sample of 287 AD patients was assessed for non-Cp-Cu serum concentrations, rs1801243, rs1061472, and rs732774 ATP7B genetic variants and the APOE4 genotype. Patients were stratified into two groups based on a non-Cp-Cu cutoff (1.9 μM). Single-locus and haplotype-group analyses were performed to define their frequencies in dependence of the non-Cp-Cu group. The two AD subgroups did not differ regarding age, sex, MMSE score, or APOE4 frequency allele, while they did differ regarding non-Cp-Cu concentrations in serum, allele, genotype, and haplotype frequencies of rs1061472 A > G and rs732774 C > T after multiple testing corrections. AD patients with a GG genotype had a 1.76-fold higher risk of having a non-Cp-Cu higher than 1.9 μmol/L (p = 0.029), and those with a TT genotype for rs732774 C > T of 1.8-fold (p = 0.018). After 100,000 permutations for multiple testing corrections, the haplotype containing the AC alleles appeared more frequently in AD patients with normal non-Cp-Cu [43 vs. 33 %; Pm = 0.03], while the haplotype containing the GT risk alleles appeared more frequently in the higher non-Cp-Cu AD (66 vs. 55 %; Pm = 0.01). Genetic heterogeneity sustains a copper AD metabolic subtype; non-Cp-Cu is a marker of this copper AD.
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