Copper and Alzheimer’s, new study opens up new scenarios on risk factors

L’Alzheimer, the most feared of dementias, affects about today 30 million people in the world (of which 600 thousand in Italy alone): a degenerative process of the brain that compromises the main cognitive functions and that remains among the diseases most in the attention of doctors and researchers in the global panorama.

A vast scientific literature over the years has supported the thesis of “bad” copper (non-ceruloplasmin) as a risk factor for Alzheimer’s disease: it is that copper also called “free” which – unlike “good” copper – does not bind to a protein, ceruloplasmin, through which it is transported into the organism to contribute to the carrying out of important vital and metabolic functions. Copper “out” of the control of proteins thus triggers oxidizing reactions that damage cells and tissues.

Today, a research (“meta-analysis”) recently published in the international journal “Biomolecules” examined 56 studies carried out between 1984 and 2020 on a total of 6,000 subjects, and compared them to a new “replication” study that analyzed several copper markers and variants of the ATP7B gene associated with its dysfunction.

“From the meta-analysis conducted it shows that in Alzheimer’s disease the presence of copper in the brain decreases, while in the blood it increases. The two data are not in contradiction with each other: they are part of a systemic imbalance between “good” copper (bound to proteins) which decreases and “bad” copper (not bound to proteins) which increases “, he explains. Rosanna Squitti, researcher at the Fatebenefratelli-Isola Tiberina in Rome and leader of the study involving 6 important Italian centers: IRCCS Centro San Giovanni di Dio-Fatebenefratelli and University of Brescia, Humanitas Institute of Milan, University of Chieti, S. Lucia Foundation-IRCCS of Rome, Mondino-IRCCS Foundation of Pavia, in addition to the Research and Laboratory Medicine Department of the Tiberina Island.

“This imbalance – continues Squitti – is the mirror of another type of pathology linked to toxic copper, Wilson’s disease, taken as a paradigm for the study of the role of metal in Alzheimer’s. The excess of non-ceruloplasmin copper increases. 3 times the risk of getting sick and the ‘replication’ study (conducted on about 170 patients) that we associated with the 56 studies examined shows that carriers of the risk variants of the ATP7B gene are more susceptible to Alzheimer’s disease “.

Not only. In line with this study, a sort of international scientific “manifesto” has been published in these days in the “Journal of Alzheimer Disease” which establishes the principle of the causal link between non-ceruloplasmin copper and Alzheimer’s and presents the scientific basis for a subtype of Alzheimer’s disease characterized precisely by the presence of this imbalance. To sign the study, with the same lead researcher Rosanna Squitti, an international “Consortium” of researchers considered prominent for this research sector: Peter Faller, (University of Strasbourg, France), Christelle Hureau (CNRS of Toulouse, France), Anthony White (QIMR Berghofer Medical Research Institute, Queensland, Australia), Alberto Granzotto (University of California, Irvine, CA, United States) and Kasper Kepp (Technical University of Denmark).

On the basis of the evidence gathered, in essence, it is summarized in a theoretical construct, from a clinical, chemical and genetic point of view, the causal link between copper and Alzheimer’s disease, even more underlined by the fact that the precursor protein of beta-amyloid, considered among the killer factors of the disease (the one that forms the plaques in the brain with Alzheimer’s) is a “copper” protein, that is, it has specific binding sites for this metal.

The study thus strengthens support for new therapeutic scenarios. “Thanks to the copper test, which can be carried out with a simple blood sample – specifies the researcher Squitti -, it is possible to identify subjects who have non-ceruloplasmin copper values ​​above the 1.6 µmol / L threshold to intervene on this factor. modifiable risk, proposing to people not yet sick a lifestyle change with a low copper content diet, while for already sick people we could propose pharmacological treatments already on the market able to reduce the presence of toxic copper, similarly to how to do with Wilson’s disease. In this regard, we have recently started a phase II clinical trial approved by AIFA and funded by the Alzheimer’s Association that will involve people with above-threshold non-ceruloplasmin copper levels and with mild cognitive impairment. to verify if drug treatment with zinc can decrease copper levels and stop the evolution of cognitive decline “.


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