A recent study has been conducted, investigating the influence of copper on a protein thought, in part, to be responsible for the onset of Alzheimer’s disease. The study, called “Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance,” was recently published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS). Could this link with copper finally explain the mystery of Alzheimer’s disease?
Copper is an essential component of the human diet, critical to a number of physiological processes. Copper possesses antioxidant function, where it scavenges for harmful free radicals, and aids in manufacture of connective tissue, neurological activity, iron mobilization, bone growth and hormone production.
The study asserts that mechanisms responsible for maintaining copper levels were disrupted in transgenic mice, which had been designed to overexpress a precursor protein, named amyloid-β precursor protein (APP). Under these auspices, the research team elected to investigate the precise mechanisms by which copper impacts upon the neurological function of mouse models.
Amyloid-β is a protein, consisting of only three to four dozen amino acids, and is produced from APP. This protein has long been associated with Alzheimer’s disease, since prominent scientific figures consider it to form plaques. The precise mechanisms of plaque-induced damage remain uncertain; however, recent research suggests it may cause disruption to glucose metabolism within brain tissue, and disrupt blood supply. Even in the healthy brain, this process is destined to take place. However, during Alzheimer’s the balance of APP production and removal is compromised, culminating in deposits of the protein across various regions of the brain.
Subsequent to testing the influence of low-levels of copper in mouse models, the study of which was led by Rashid Deane of the University of Rochester Medical Center, the team posited the following:
- Copper enters the brain through copper transporters (Ctrl and DMT1 and ATP7A)
- Copper amasses around capillaries of the brain
- A transporter protein (LRP1), responsible for transportation of Aβ across the blood brain barrier, became altered and degraded
- Copper can induce protein oxidation and lipid peroxidation, which may then go on to interact with the offending proteins, such as APP and Aβ
- A reaction between Copper and Aβ could cause the production of damaging reactive oxygen species, which may contribute towards cellular damage in Alzheimer’s
- Copper may encourage formation of insoluble structures of Aβ
These findings seem to implicate copper heavily in the pathology of Alzheimer’s onset, and perhaps go a long way to explaining a mystery that has eluded scientists for so long.
Essentially, the break-down of LRP1 impairs removal of harmful Aβ protein. This protein then accumulates to form plaques, an event that may also be sped up by the existence of copper. These plaques can no longer be removed by the protective mechanisms of the brain, impeding neurological function.
The blood brain barrier (BBB) is also affected, during the latter stages of copper exposure. The BBB is a protective layer that prevents dangerous substances from entering the brain, acting as a filter. The authors allege copper to be responsible for causing the BBB to become leaky.
According to RedOrbit, a member of the Center for Translational Neuromedicine (CTN) made his feelings on the subject quite transparent:
“It is clear that, over time, copper’s cumulative effect is to impair the systems by which amyloid beta is removed from the brain… This impairment is one of the key factors that cause the protein to accumulate in the brain and form the plaques that are the hallmark of Alzheimer’s disease.”
Research, prior to Deane’s work, has also revealed a link between Alzheimer’s and copper accumulation. Studies that have dosed rabbit models with small quantities of copper result in a concomitant accumulation of amyloid-β around cerebral tissue and blood vessels.
However, this conflicts with other reports, which seem to suggest copper is able to inhibit amyloid-β production mechanisms, in vitro. These findings have been corroborated by scientific study on live mouse models, which were genetically altered to overexpress APP, where the introduction of copper actually reduced soluble amyloid-β levels.
This also raises an interesting question, however. If copper is so ubiquitous, found in drinking water and a host of food products, and is very much necessary for proper physiological functioning, what can be done to lessen its impact on Alzheimer’s disease progression, assuming its involvement to be true? Deane advised individuals to continue consuming their recommended amount of dietary copper, but cautioned against having too much.
Judging by these results, there certainly appears to be a link between the onset of Alzheimer’s disease and copper, at least in mouse models. How these results can be implemented practically, however, when copper remains such a vital part of the population’s diet, remains to be seen. What is more, the presence of highly conflicting studies would suggest that the mystery of Alzheimer’s disease is not completely explained, just yet.
By: James Fenner