Alzheimer’s: Copper transport in blood provides fresh clues

Faulty regulation of copper levels in tissues plays a significant role in a wide selection of illnesses, including Alzheimer’s disease, Parkinson’s disease, and motor neuron disease. An investigation of molecules that carry copper in the bloodstream has provided new leads for diagnosis and treatment.

The metal copper is crucial for a wholesome metabolism, yet, scientists know surprisingly little about how precisely your body transports it and maintains optimum levels in tissues.

Bonded to protein molecules, copper is a essential component of numerous enzymes that catalyze key metabolic reactions.

“Biochemists have known about the importance of copper in the human body for years, but even they don't know, for instance, how this component reaches from our food to the right destinations, i.e., various copper enzymes,” says Prof. Peep Palumaa, head of the study Band of Metalloproteomics at Tallinn University of Technology in Estonia.

Copper exists in trace amounts throughout the body. The best concentrations occur in parts of the body which may have extremely high activity, including the liver, brain, heart, kidneys, and skeletal muscle.

Multiple roles

Among its many roles, the metal is vital for generating energy during cell respiration, making red blood cells, mounting immune responses, and maintaining nerve cells.

In excess, however, it could trigger the production of destructive free radicals and contribute to inflammation.

Research has linked the faulty regulation of copper levels to many neurodegenerative illnesses, including Menkes syndrome, motor neuron disease, Parkinson’s disease, and Alzheimer’s disease.

A report that Medical News Today reported on in 2013, for instance, discovered that when copper accumulates in the mind, it promotes the development of the beta-amyloid plaques that are the hallmark of Alzheimer’s disease.

The study discovered that copper not merely inhibits removing soluble beta-amyloid molecules from the mind but also encourages them to clump together to create insoluble plaques.

Biochemists have been trying to get a much better grasp of the way the body maintains optimum levels of copper in its tissues and what goes on when this homeostatic process goes awry.

The knowledge may help them develop new methods to diagnose, monitor, and treat diseases that involve the break down of copper homeostasis.

As part of this endeavor, Prof. Palumaa and his colleagues wanted to determine how copper is transported around your body in the bloodstream.

Unusually for science, they learned that the procedure was simpler than that they had expected. Previously, biochemists believed that three proteins play a role in transporting copper, but, in line with the new study, only 1 is a significant player.

Affinity for copper

To measure each protein’s affinity for copper - meaning how tightly it binds to copper ions - the researchers developed a fresh and progressive approach called liquid chromatography and ICP-MS (inductively coupled plasma mass spectrometry). These biochemical techniques separate and identify molecules that can be found in trace amounts in a biological fluid, such as for example blood or cerebrospinal fluid.

The scientists found that in the blood, about 75% of copper ions are bound to an enzyme called ceruloplasmin, while about 25% are bound to an enzyme called albumin.

However, ceruloplasmin binds to copper so tightly that it's unlikely to are likely involved in transporting the metal to where it really is needed. The enzyme’s main job is apparently helping another protein transport iron in the blood.

Albumin, on the other hand, binds to copper significantly less strongly and may very well be the main copper transporter.

The researchers discovered that a tiny proportion of copper in the blood (about 0.2%) also binds to an amino acid called histidine. They speculate that histidine acts as a catalyst, helping release copper from albumin when it reaches a destination including the liver.

Biochemists had assumed that a further protein, called alpha-2 macroglobulin, also transports copper. However, Prof. Palumaa and his colleagues report that within their experiments, it didn't bind to copper in blood plasma in significant quantities.

Regulating copper levels

The research is a product of collaboration between scientists at Tallinn University of Technology and the Swedish pharmaceutical company Wilson Therapeutics AB.

Wilson Therapeutics AB’s lead product is Decuprate, that is a promising therapeutic agent to take care of Wilson’s disease, a rare genetic disorder that causes copper to build up in toxic quantities in the liver, brain, and other tissues.

By binding to copper, Decuprate promotes its excretion from the body.

In their paper, Prof. Palumaa and his colleagues say that their findings will make it possible to find the disturbances in copper metabolism that characterize diseases such as for example Wilson’s and Alzheimer’s.

Their research may possibly also provide new methods to monitor the effectiveness of drugs such as for example Decuprate in regulating copper levels.

“[Our] research findings can be utilised for various applications. First, they help to understand the normal copper metabolism in your body, which has a direct diagnostic value. Second, these results also help identify disturbances in the body’s copper metabolism. The latter occur in a number of genetic diseases, such as Wilson’s and Menkes disease, together with the most frequent neurodegenerative disease - Alzheimer’s disease.”

- Prof. Peep Palumaa

He continues, “Furthermore to specific diagnoses, the result of pharmaceuticals normalizing copper metabolism that are being used for the treating the abovementioned diseases may also be monitored through copper equilibrium in blood.”