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Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study.
Curr Alzheimer Res 2017; 14(12):1318-1326CA

Abstract

BACKGROUND

Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype.

OBJECTIVE

In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off.

METHOD

We assessed levels of copper, ceruloplasmin, non-Cp Cu, cerebrospinal levels of total Tau protein (h-tau), Thr 181 phosphorylated tau protein (P-tau) and β-amyloid 1-42, and APOE4 genotype in 66 AD patients and compared neuroimaging indices of a visual rating scale of cerebral atrophy and neurovascular burden in AD patients stratified in 'Normal' and 'High' non-Cp Cu groups.

RESULTS

The stratification for non-Cp Cu originated AD groups which did not differ for medial temporal lobe atrophy, periventricular hyperintensities, deeper hyperintensities (including frontal, parietooccipital and temporal white matter hyperintensities), infratentorial hyperintensities indices, while they differed for global atrophy. More specifically, AD patients within the high non-Cp Cu group had a less severe burden of global atrophy (p=0.042).

CONCLUSION

This neuroimaging heterogeneity between AD groups is suggestive of the existence of a copper metabolic subtype of AD; non-Cp Cu appears a good marker of this copper AD.

Authors+Show Affiliations

Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio- Fatebenefratelli, 25125 Brescia. Italy.Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome. Italy.Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome. Italy.Department of Radiology, Fatebenefratelli Hospital, Rome. Italy.Department of Laboratory Medicine, Research and Development Division, Fatebenefratelli Hospital, Isola Tiberina, Rome. Italy.Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome. Italy.Don Carlo Gnocchi ONLUS Foundation, Milan. Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28669331

Citation

Squitti, Rosanna, et al. "Patients With Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: a Neuroimaging Study." Current Alzheimer Research, vol. 14, no. 12, 2017, pp. 1318-1326.
Squitti R, Simonelli I, Cassetta E, et al. Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study. Curr Alzheimer Res. 2017;14(12):1318-1326.
Squitti, R., Simonelli, I., Cassetta, E., Lupoi, D., Rongioletti, M., Ventriglia, M., & Siotto, M. (2017). Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study. Current Alzheimer Research, 14(12), pp. 1318-1326. doi:10.2174/1567205014666170623125156.
Squitti R, et al. Patients With Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: a Neuroimaging Study. Curr Alzheimer Res. 2017;14(12):1318-1326. PubMed PMID: 28669331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study. AU - Squitti,Rosanna, AU - Simonelli,Ilaria, AU - Cassetta,Emanuele, AU - Lupoi,Domenico, AU - Rongioletti,Mauro, AU - Ventriglia,Mariacarla, AU - Siotto,Mariacristina, PY - 2017/02/23/received PY - 2017/04/13/revised PY - 2017/06/24/accepted PY - 2017/7/4/pubmed PY - 2018/6/22/medline PY - 2017/7/4/entrez KW - Alzheimer's disease KW - Neuroimaging heterogeneity KW - copper not bound to ceruloplasmin (non-Cp Cu) KW - copper. KW - free copper KW - global atrophy SP - 1318 EP - 1326 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 14 IS - 12 N2 - BACKGROUND: Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype. OBJECTIVE: In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off. METHOD: We assessed levels of copper, ceruloplasmin, non-Cp Cu, cerebrospinal levels of total Tau protein (h-tau), Thr 181 phosphorylated tau protein (P-tau) and β-amyloid 1-42, and APOE4 genotype in 66 AD patients and compared neuroimaging indices of a visual rating scale of cerebral atrophy and neurovascular burden in AD patients stratified in 'Normal' and 'High' non-Cp Cu groups. RESULTS: The stratification for non-Cp Cu originated AD groups which did not differ for medial temporal lobe atrophy, periventricular hyperintensities, deeper hyperintensities (including frontal, parietooccipital and temporal white matter hyperintensities), infratentorial hyperintensities indices, while they differed for global atrophy. More specifically, AD patients within the high non-Cp Cu group had a less severe burden of global atrophy (p=0.042). CONCLUSION: This neuroimaging heterogeneity between AD groups is suggestive of the existence of a copper metabolic subtype of AD; non-Cp Cu appears a good marker of this copper AD. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/28669331/Patients_with_Increased_Non_Ceruloplasmin_Copper_Appear_a_Distinct_Sub_Group_of_Alzheimer's_Disease:_A_Neuroimaging_Study_ L2 - http://www.eurekaselect.com/153609/article DB - PRIME DP - Unbound Medicine ER -