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Copper exposure likely ‘key player’ in Alzheimer’s

U. ROCHESTER (US) — Copper, found in a variety of foods and some drinking water, may be one of the main environmental factors that trigger the onset and enhance the progression of Alzheimer’s disease.

Copper’s presence in the food supply is ubiquitous. It is found in drinking water carried by copper pipes, nutritional supplements, and in certain foods such as red meats, shellfish, nuts, and many fruits and vegetables.

The metal plays an important and beneficial role in nerve conduction, bone growth, the formation of connective tissue, and hormone secretion, but new research shows that even low levels can contribute to Alzheimer’s by preventing the clearance and accelerating the accumulation of toxic proteins in the brain.

“It is clear that, over time, copper’s cumulative effect is to impair the systems by which amyloid beta is removed from the brain,” says Rashid Deane, a research professor of neurosurgery at the University of Rochester Medical Center.

“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.”

A new study published in the Proceedings of the National Academy of Sciences shows copper can accumulate in the brain and cause the blood brain barrier—the system that controls what enters and exits the brain—to break down, resulting in the toxic accumulation of the protein amyloid beta, a by-product of cellular activity.

Using both mice and human brain cells, Deane and colleagues conducted a series of experiments that have pinpointed the molecular mechanisms by which copper accelerates the pathology of Alzheimer’s disease.

Under normal circumstances, amyloid beta is removed from the brain by a protein called lipoprotein receptor-related protein 1 (LRP1). These proteins—which line the capillaries that supply the brain with blood—bind with the amyloid beta found in the brain tissue and escort them into the blood vessels where they are removed.

The research team “dosed” normal mice with copper over a three month period. The exposure consisted of trace amounts of the metal in drinking water and was one-tenth of the water quality standards for copper established by the Environmental Protection Agency. “These are very low levels of copper, equivalent to what people would consume in a normal diet.” Deane says.

The researchers found that the copper made its way into the blood system and accumulated in the vessels that feed blood to the brain, specifically in the cellular “walls” of the capillaries.

These cells are a critical part of the brain’s defense system and help regulate the passage of molecules to and from brain tissue.  In this instance, the capillary cells prevent the copper from entering the brain. However, over time the metal can accumulate in these cells with toxic effect.

The researchers observed that the copper disrupted the function of LRP1 through a process called oxidation which, in turn, inhibited the removal of amyloid beta from the brain. They observed this phenomenon in both mouse and human brain cells.

‘Leaky’ barrier

They then looked at the impact of copper exposure on mouse models of Alzheimer’s disease. In these mice, the cells that form the blood brain barrier have broken down and become “leaky”—a likely combination of aging and the cumulative effect of toxic assaults—allowing elements such as copper to pass unimpeded into the brain tissue.

The copper stimulated activity in neurons that increased the production of amyloid beta. The copper also interacted with amyloid beta in a manner that caused the proteins to bind together in larger complexes creating logjams of the protein that the brain’s waste disposal system cannot clear.

This one-two punch, inhibiting the clearance and stimulating the production of amyloid beta, provides strong evidence that copper is a key player in Alzheimer’s disease.

In addition, the researchers observed that copper provoked inflammation of brain tissue which may further promote the breakdown of the blood brain barrier and the accumulation of Alzheimer’s-related toxins.

However, because metal is essential to so many other functions in the body, the researchers say that these results must be interpreted with caution.

“Copper is an essential metal and it is clear that these effects are due to exposure over a long period of time,” Deane says. “The key will be striking the right balance between too little and too much copper consumption. Right now we cannot say what the right level will be, but diet may ultimately play an important role in regulating this process.”

The Alzheimer’s Association, National Institute on Aging, and National Institute of Environmental Health Sciences funded the study.

Source: University of Rochester

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7 Comments

  1. Ann Fonfa

    Folks, this is so silly. Copper in food is not causing Alzheimer’s Disease. This is typical BLIND research where when ONLY one thing is looked at, it is found. But silly conclusion.

    Food is balanced. If one eats fruits and vegetables – unless the eating habit is JUST one food, it is considered balanced. Recently people with diabetes have finaly been given the green light to eat fruits because they are FOOD ot SUGAR. Common sense.

    Copper pipes could certainly be a contributing factor. But to put food on the same level, uh uh.

    I am an advocate for people with cancer, founder of the Annie Appleseed Project.. I use a broad and general gathering of information to form conclusions and I believe this balance is MISSING in research.

  2. scott

    Ann, and her organization, is an alternative medicine nut job. The article CLEARLY states that copper is essential and the findings must be interpreted with caution. Some foods retain certain minerals more than others. The research didn’t condemn any foods, it merely listed foods that contain higher amounts of copper. Further research is needed to determine what it’s too much copper. Other research could look into how much copper gets into organic systems through man-made sources.

  3. Teresa Martin Klaiber

    I did not take the article as pointing directly at food. With a great grandmother, grandmother, mother and aunt all raised in the same house I tended to wonder about what in the enviro might have an effect – what were the pipes in that house – what did they cook with – copper pans? – yes my mother wore copper jewl. Did the other females? I have read so many theories that I toss out daily – sitting here now caring for my mother who can’t tell what, who, where – this definitely needs further research.

  4. Gary

    First, I have a few choice things to say to scott for his comment, but I think his attitude speaks for itself.
    Second, a rather famous MD by the name of Carl Pfieffer, who wrote a number of popular books such as “Zinc and other Micronutrients” mentioned that when galvanized pipes were replaced with copper piping because the steel in the galvanized pipe was being converted into battleships for WWII, he noticed an upswing in the incidence of bipolar activity in his patients. And, as he stated in the aforementioned book, zinc (used in galvanized pipe) balances copper. When there is not enough zinc to balance copper and copper accumulates. Here’s one (out of many) citations from PubMed – http://www.ncbi.nlm.nih.gov/pubmed/23948932 – that supports the premise. If that doesn’t satisfy scott, then I suggest he take a look through the 755 other references related to zinc, copper and Alzheimers.

  5. webhelp

    Has anyone considered that for a very long time that copper pipe was installed with lead based solder, and only recently has code been revised to require the use of lead free (95/5 tin/antimony) solder for copper pipe installation.?

  6. Bryan

    The article reports nothing at all new. Similar research was reported nearly a decade ago:

    Bellingham SA, Lahiri DK, Maloney B, La Fontaine S, Multhaup G, Camakaris J.
    J Biol Chem. 2004 May 7;279(19):20378-86. Epub 2004 Feb 25.
    Copper depletion down-regulates expression of the Alzheimer’s disease amyloid-beta precursor protein gene.

  7. Mitch

    Gary,
    FYI, copper was and is a considerably scarcer and more strategic metal than was/is steel. The story you relate is farfetched at best since the US mint used zinc on minting pennies during WWII. The purpose was to reduce non war use of copper.

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