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Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and predictive value of non-ceruloplasmim copper in mild cognitive impairment conversion to full AD
Squitti R.. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2014-07-10
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Alzheimer's disease (AD) is the most common form of dementia. A myriad of complex factors contribute to AD, promoting the deposition in plaques of amyloid-beta (Aβ), which is the main constituent of this pathognomonic sign of AD at autopsy brain inspection. Aβ toxicity is related to oxidative stress, which results in synaptic loss in specific brain areas, eventually leading to cognitive decline. Metal, and especially copper, dyshomeostasis is a key factor in these processes. Recent studies have demonstrated that the serum fraction of copper that is not bound to ceruloplasmin (Non-Cp copper, also known as 'free' or labile copper) increases in a percentage of AD patients and mild cognitive impairment (MCI) subjects; this is considered a precursor of AD. Non-Cp copper is the exchangeable fraction of low molecular weight copper in serum. It is distinguished from the copper structurally bound to the ceruloplasmin protein, a master protein of iron metabolism. Non-Cp copper levels are higher than normal reference values (range 0-1.6μmol/L) in about 50% of amnestic MCI subjects and 60% of AD patients, typifying them in a subset of AD. Meta-analyses, genetic studies and a prognostic study evaluating the predictive value of Non-Cp copper in MCI conversion to full AD demonstrate the existence of this copper phenotype of AD.
What this study adds
Evidence grade: High
This is a pooled review. This review argues for a 'copper subtype' of Alzheimer's, based on copper in the blood that is not bound to the protein ceruloplasmin. Such free copper is reported above normal reference values in about 50% of people with amnestic mild cognitive impairment and 60% of people with Alzheimer's.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Squitti, R. (2014). Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and predictive value of non-ceruloplasmim copper in mild cognitive impairment conversion to full AD. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). https://doi.org/10.1016/j.jtemb.2014.06.018
Vancouver
Squitti R. Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and predictive value of non-ceruloplasmim copper in mild cognitive impairment conversion to full AD. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2014. doi:10.1016/j.jtemb.2014.06.018. PMID: 25066791.
BibTeX
@article{squitti2014-25066791,
author = {Squitti, R.},
title = {{Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and predictive value of non-ceruloplasmim copper in mild cognitive impairment conversion to full AD}},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
year = {2014},
doi = {10.1016/j.jtemb.2014.06.018},
pmid = {25066791},
url = {https://doi.org/10.1016/j.jtemb.2014.06.018}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Aβ toxicity is related to oxidative stress, which results in synaptic loss in specific brain areas, eventually leading to cognitive decline.
- Recent studies have demonstrated that the serum fraction of copper that is not bound to ceruloplasmin (Non-Cp copper, also known as 'free' or labile copper) increases in a percentage of AD patients and mild cognitive impairment (MCI) subjects; this is considered a precursor of AD.
Why it matters
This review argues for a 'copper subtype' of Alzheimer's, based on copper in the blood that is not bound to the protein ceruloplasmin. Such free copper is reported above normal reference values in about 50% of people with amnestic mild cognitive impairment and 60% of people with Alzheimer's. The authors say meta-analyses, genetic studies and a prognostic study support this copper phenotype, which suggests a possible way to identify a subset of patients.
Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 53/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)) |
| Journal's citation record | 1 / 4 | Journal of Trace Elements in Medicine and Biology: journal h-index 114 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | 4 / 7 | Cited 49 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 3 / 6 | Cited 3.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rosanna Squitti: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele: institution h-index 393 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25066791) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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