Quite often, modern scientists toil for decades only to discover something that our ancestors knew all along from observation and keen intuition. Even after the essential discovery is made, it may take years before the official health guidelines catch up with the scientific research. It is because of this that copper, an absolutely essential element for human health, has only recently started to attract the attention of nutrition gurus. Still today, not many people know that they are at risk of copper deficiency which may put them in danger of many illnesses, not to mention accelerated aging of skin and hair.

The slow process of recognizing the importance of copper was best highlighted by Dr. Leslie Klevay in his paper published in 1996 [“Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations about copper”, Klevay & Medeiros 1996]. He reviewed the last 10 editions of the Recommended Daily Allowances (RDAs) guidelines and observed that in the 1943 edition the recommended daily amount of copper was estimated at 1-2 mg/day, and in a 1958 edition (15 years later), it was stated that “2 mg/day will maintain adults in balance”.

In the same 1958 edition, he found a statement that mentioned “a typical diet” usually supplies 2-5 mg of copper a day, and that the deficiency of this metal is very rare. However, in the 1989 edition, we see a reference to the National Food Consumption survey conducted in 1987-1988, according to which an average intake of copper was 1.2 mg/day for males and only 0.9 mg/day for females—a statistic well below the recommended 2mg/day. In this same edition it was also stated that copper intake as high as 3 mg/day may be necessary to maintain good health. The current RDI (Recommended Dietary Intake established by the U.S. Food and Drug Administration) for copper is 2 mg/day.

 

Another reference that should be considered is the estimated safe and adequate daily dietary intakes or ESADDI (Natural Research Council, 1989) which recommends a daily intake of 1.5-3 mg of copper. Recently, U.S. dietary guidelines underwent another major revision and RDAs were replaced by The Dietary Reference Intakes (DRI) established by the Food and Nutrition Board of the Institute of Medicine, 1997-2001. The World Health Organization gives 10 mg/day as the tolerable upper limit of copper intake.

Copper deficiency

Out of the blue, the recommended intake of copper was set up as 0.9 mg/day —a number that is clearly not enough to assure adequate copper intake! For example, a paper published in 2010 by Chambers et al studied the effects of copper deficiency and excess. This study came to the conclusion that to prevent copper deficiency optimum intake for copper should be 2.6 mg/day (which is well below the level where any adverse effects can be seen).

 

The sudden drop in the recommended intake of copper is more interesting when you take into consideration that estimated daily loss of copper is about 1.3 mg/day. This is one of the reasons why it is so dangerous to lower copper consumption below 2 mg/day (Williams 1983). Active males should also be aware that additional daily loss of copper due to sweating may be as high as 0.34 mg/day ( Jacob 1981).

But is copper really that important and worth such an in depth discussion? Absolutely! In fact, copper deficiency may be a leading cause of many so-called “diseases of civilizations” that currently plague the population in the United States. Furthermore it may also be the main reason why our skin and hair lose their health and vitality as we age.

 

Since copper peptides of course contain copper, many ask about the function of copper within the body. As they learn about how copper works and experience its benefits, they also want to know about its safety.

 

Copper is an essential metal necessary for many processes in the human body. A deficiency in copper can contribute to a host of health problems, including a higher rate of: cellular oxidation, cancer, cardiovascular disease, atherosclerosis, LDL “bad cholesterol”, lipid oxidation, aortic aneurysms, osteoarthritis, rheumatoid arthritis, osteoporosis, chronic conditions involving bone and connective tissue, brain defects in newborns, obesity, graying of hair, sensitivity to pain, Alzheimer’s disease, reproductive problems, depression, and fatigue; as well as lowering HDL “good cholesterol”, reduction in the pleasure producing brain enkephalins, and impaired brain function.

Original Post

Kirsten and Jessica,

 

Do be careful with the Brazil Nuts.  You can google for the details if you want but Brazil Nuts have the highest amount of selenium in them than any other food.  As a matter of fact they have SO much that believe it or not (I was shocked when I learned of this) you can actually get an overdose of selenium form eating too many Brazil Nuts.  I forget the amount they have but it is exorbanant compared to other foods.  If I'm remembering correctly you really shouldn't eat more than 2 or 3  at a time and not every day to avoid selenium overdose in the body.  If only all vitamins were that compact that you only needed to eat a few bites and satisfy your nutritional needsfor the day lol!  
http://www.drweil.com/drw/u/ART02870/selenium.html
     

Originally Posted by Kirsten:

Can you share which foods are naturally high in copper that we should be incorporating into our diets? 

According to this article by Dr. Andrew Weil some foods are:

How do you get enough copper from foods?
Good food sources include vegetables, legumes, beans, nuts and seeds, mushrooms, shellfish (especially cooked oysters), avocado and whole grains.

Also too much zinc or iron can lower the copper in your body.  Also:
Are there any other special considerations?
Boron, vitamin C, selenium, manganese and molybdenum can affect levels of copper in the body. Zinc can lower copper stores, so it is often recommended to take supplemental copper (at a ratio of 1 to 10) if you take supplemental zinc.

The above is all from the article cited below.  There are more articles on the site as well about copper and everything else medically related. Like Dr. Pickart, Dr. Weil is my mentor and the person I turn to when I need answers as I trust pure science and those who have studied and understand it.  For my medical issues I check out Dr. Weil and what he has to teach me about it, and for my skin issues I turn to dr. Pickart. 
(Like I used to think hyaluronic acid was good for my skin but now I understand thanks to Dr. Pickart that it breaks down the skin barrier so is not at all good for the skin!)  I stopped using it as much as is possible as so many products include it in their ingredients.  And other things like that - I am learning so much about skincare I can't believe it myself!)    


http://www.drweil.com/drw/u/ART02871/copper.html





Dear Beth, 

 

Many of our clients have emailed us with concerns about the safety of copper. Excessive copper has been blamed for many diseases – Alzheimer's, heart disease, cancer, etc. The problem is that most of this comes from data on blood plasma copper and diseases. But usually, high blood plasma copper is associated with low tissue copper. Most plasma copper (60%) is locked in proteins such as in ceruloplasmin  - an acute phase reactant that rises with stress and disease, and other proteins such as transcuprein. Copper that is rapidly available to the tissues is about 10% of the plasma copper that is on albumin. Another problem is that many studies are conducted on mice or other animals. In every case so far, when all the data came in on a disease, it was found that higher tissue copper reduced the disease or condition.

Actual human studies have concluded that higher copper protects the brain tissue and that copper did not worsen Alzheimer's. Studies in laboratory animals has been more in conflict.

Newer studies have found that more copper 2+ blocks the formation of plaques. On the other hand, many researchers believe that plaque formation does not cause Alzheimer's.

 

One good human study is worth more than 100,000 mouse studies.

See studies below.

 

Human Studies

1. In this placebo-controlled study 68 AD patients (34 control, 34 high copper) put on 8 mgs daily copper (a high amount) for 1 year. There was no negative finding.A predictive protein marker of CSF Abeta42 is lower in persons developing Alzehiemer's and the extra copper maintained this protein at a higher level, a possible anti-Alzheimer's effect. 

 

J Neural Transm. 2008 Dec;115(12):1651-9. Epub 2008 Oct 30.
Effect of copper intake on CSF parameters in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial.
Kessler H, Pajonk FG, Bach D, Schneider-Axmann T, Falkai P, Herrmann W, Multhaup G, Wiltfang J, Schäfer S, Wirths O, Bayer TA.
Department of Psychiatry and Psychotherapy, Saarland University Hospital, Homburg/Saar, Germany.


A plethora of reports suggest that copper (Cu) homeostasis is disturbed in Alzheimer's disease (AD). In the present report we evaluated the efficacy of oral Cu supplementation on CSF biomarkers for AD. In a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial (12 months long) patients with mild AD received either Cu-(II)-orotate-dihydrate (verum group; 8 mg Cu daily) or placebo (placebo group). The primary outcome measures in CSF were Abeta42, Tau and Phospho-Tau. The clinical trial demonstrates that long-term oral intake of 8 mg Cu can be excluded as a risk factor for AD based on CSF biomarker analysis. Cu intake had no effect on the progression of Tau and Phospho-Tau levels in CSF. While Abeta42 levels declined by 30% in the placebo group (P = 0.001), they decreased only by 10% (P = 0.04) in the verum group. Since decreased CSF Abeta42 is a diagnostic marker for AD, this observation may indicate that Cu treatment had a positive effect on a relevant AD biomarker. Using mini-mental state examination (MMSE) and Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) we have previously demonstrated that there are no Cu treatment effects on cognitive performance, however. Finally, CSF Abeta42 levels declined significantly in both groups within 12 months supporting the notion that CSF Abeta42 may be valid not only for diagnostic but also for prognostic purposes in AD.

 

2.This study suggests low brain copper is associated with plaque formation in humans. Actual studies of human brains are the best evidence. The healthiest brain areas had the most copper.

 

J Alzheimers Dis. 2012;31(4):725-730. Brain burden areas of aluminum, iron, and copper and their relationships with amyloid-β pathology in 60 human brains. Exley C, House E, Polwart A, Esiri MM. Lennard-Jones Laboratories, The Birchall Centre, Keele University, Staffordshire, UK.

 

The deposition in the brain of amyloid-β as beta sheet conformers associated with senile plaques and vasculature is frequently observed in Alzheimer’s disease. While metals, primarily aluminum, iron, zinc, and copper, have been implicated in amyloid-β deposition in vivo, there are few data specifically relating brain metal burden with extent of amyloid pathologies in human brains. Herein brain tissue content of aluminum, iron, and copper are compared with burdens of amyloid-β, as senile plaques and as congophilic amyloid angiopathy, in 60 aged human brains. Significant observations were strong negative correlations between brain copper burden and the degree of severity of both senile plaque and congophilic amyloid angiopathy pathologies with the relationship with the former reaching statistical significance. While we did not have access to the dementia status of the majority of the 60 brain donors, this knowledge for just 4 donors allowed us to speculate that diagnosis of dementia might be predicted by a combination of amyloid pathology and a ratio of the brain burden of copper to the brain burden of aluminum. Taking into account only those donor brains with either senile plaque scores ≥4 and/or congophilic amyloid angiopathy scores ≥12, a Cu:Al ratio of <20 would predict that at least 39 of the 60 donors would have been diagnosed as suffering from dementia. Future research should test the hypothesis that, in individuals with moderate to severe amyloid pathology, low brain copper is a predisposition to developing dementia.

 

3. In brain plaques from persons with Alzeheimer's disease, iron and aluminum appear to cause plaque formation while copper and zinc do not.


Exley, C. 2006. “Aluminium and Iron, but Neither Copper nor Zinc, Are Key to the Precipitation of Beta-sheets of Abeta_{42} in Senile Plaque Cores in Alzheimer’s Disease.” J Alzheimers Dis 10 (November): 173–7. 17119286.
Birchall Centre for Inorganic Chemistry and Materials Science, Keele University, Staffordshire, UK.

 

A number of metals including Fe(II)/Fe(III), Al(III), Zn(II) and Cu(II) are found co-localised with beta-sheets of Abeta_{42} in senile plaque cores in AD brain. We know neither why nor how the co-localisation takes place or, indeed, if it is entirely aberrant or partly protective. There are data from in vitro studies which may begin to explain some of these unanswered questions and in considering these I have summised that Al(III) and Fe(III)/Fe(II) are directly involved in the precipitation of beta-sheets of Abeta_{42} in senile plaque cores whereas the presence of Cu(II) and Zn(II) is adventitious. The co-deposition of Al(III), Fe(III) and beta-sheets of Abeta_{42} could act as a source of reactive oxygen species and begin to explain some of the oxidative damage found in the immediate vicinity of senile plaques. Whether such metal-Abeta_{42} synergisms are an integral part of the aetiology of AD remains to be confirmed.

 

4. Low serum copper in Alzheimer's patients correlates low cognitive ability.

 

J Alzheimers Dis. 2005 Sep;8(1):23-7.

Cognitive decline correlates with low plasma concentrations of copper in patients with mild to moderate Alzheimer's disease. Pajonk FG, Kessler H, Supprian T, Hamzei P, Bach D, Schweickhardt J, Herrmann W, Obeid R, Simons A, Falkai P, Multhaup G, Bayer TA. Department for Psychiatry, Saarland University, Building 90, 66421 Homburg/Saar, Germany.

 

Alzheimer's disease (AD) is a devastating brain disorder clinically characterised by progressive loss of characteristic cognitive abilities. Increasing evidence suggests a disturbed copper (Cu) homeostasis to be associated with the pathological processes. In the present study we analysed the plasma Cu levels and cognitive abilities using the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog) in 32 patients with mild to moderate AD. Statistical analysis revealed a negative correlation between plasma Cu levels and cognitive decline (r=-0.49; P<0.01). Patients with low plasma Cu (mean 82 +/- SD 9) had significant higher ADAS-cog values (mean 23 +/- SD 7), than patients with medium plasma Cu (mean 110 +/- SD 7), who exhibited lower ADAS-cog scores (mean 16 +/- SD 4; ANOVA, P<0.0001). Despite the fact that all patients had plasma Cu levels within the physiological range between 65 microg and 165 microg/dL, 87.5% of the patients revealed a significant negative correlation between plasma Cu and ADAS-cog. This finding supports the hypothesis of a mild Cu deficiency in most AD patients.

5. How much copper do humans need each day? The recommended RDA for copper is 0.7 mgs/day. The following study put men on a low copper diet of 1.03 mgs/day. Within 8 weeks, 4 of the 24 subjects had serious heart issues ranging from myocardial infarction to arrhythmia. This means that if you take the RDA of copper you will probably have serious health problems.

 

Am J Clin Nutr. 1985 Aug;42(2):242-51.Indices of copper status in humans consuming a typical American diet containing either fructose or starch.Reiser S, Smith JC Jr, Mertz W, Holbrook JT, Scholfield DJ, Powell AS, Canfield WK, Canary JJ.

 

Twenty-four male subjects originally participated in a study to determine the effects of feeding diets comparatively low in copper (1.03 mg/day/2850 kcal) and containing either 20% fructose or starch on indices of copper status. During the course of feeding the diets for 11 wk, four of the subjects exhibited heart-related abnormalities and were removed from the study. Fructose ingestion had no effect on serum ceruloplasmin activity or serum copper concentration but did significantly reduce cuprozinc superoxide dismutase (SOD) activity of erythrocytes as compared to starch. Repletion of the subjects with 3 mg copper/day for 3 wk significantly increased SOD levels in subjects previously fed fructose but not starch. Apparent copper balance was significantly greater when the subjects consumed the fructose as compared to the starch diet. These results suggest that the type of dietary carbohydrate fed can differentially affect indices of copper status in humans.

 

6. Copper and Anti-oxidant actions.

 

Alzeheimer's is considered result of excessive oxidations in the brain. Human studies found the greatest anti-oxidant activity in persons given 6 mgs/day supplemental copper. Look at http://skinbiology.com/copper-...antiaging-metal.html

 

7. GHK actions on gene expression of Alzheimer's related genes.

 

The copper carrying molecule GHK may possibly inhibit Alzheimer's. GHK increases gene expression of the LRP1 gene by 3.49 fold. A lack of the LRP1 gene expression is thought to be a causal factor in Alzheimer's. A lack of LRP1 damages neurons by starving them of cholesterol. Also, Interleukin 18 is very inflammatory considered a possible cause of Alzheimer's. GHK increases the expression of the Interleukin 18 binding protein (IL18BP) 3.95 fold and this inhibits Interleukin 18. High levels of the blood protein APOE is considered a cause of Alzheimer's and GHK suppresses gene expression of the APOE gene by 2.07 fold. 

 

8. Loren Pickart's brain and GHK.

 

If copper caused Alzheimer's or Dementia, I would have been gone long ago since I have used the skin products for many years. I was planning to retire at 65 but now am 75 and doing my best work. We are starting to publish on GHK's anti-cancer actions first found at two universities.  We found GHK's inducing anti-cancer actions on over 80 genes. Then we will publish detailed gene data on GHK as the best potential treatment for COPD (first found at 4 universities) and also publish some very good data on GHK's positive effects on genes important in human aging.

 

8. Copper uptake from copper peptides.

 

Previously, we had studies performed on the penetration of GHK-copper through human cadaver skin (from people who donated their body for medical research at UCSF). The penetration through the skin of GHK-copper was 0.14% or 0.0014 of the applied peptide. After all the calculations for the amount of copper in GHK-copper (16%), the amount of copper in 1 gram in a 3% GHK cream (0.0048 grams), and the passage through the skin (multiply times 0.0014), it comes out that 7 micrograms of copper should enter the body. Even if the uptake is 10 times that amount enters the body it is still only 70 micrograms of copper or 0.07 milligrams.

During FDA required safety tests on GHK-copper for studies on human skin ulcers, the copper peptide was repeatedly applied in large amounts to wounds in rats and rabbits by an independent safety-testing company and they never observed a rise in blood copper (which surprised me).

 

Animal studies

Animal studies are in conflict. Laboratory animals are highly inbred and different animal strains may give different results and may not reflect human results. Two studies found more copper reduced brain plaque formation and two other studies said that more copper increased plaque formation. One study fed rabbits cholesterol and copper and reported more plaque formation but rabbits never naturally eat cholesterol containing foods. Another said copper salts were added to water and this increased plaque formation in a strain of mice. But copper is never taken in as pure copper ion, it is chelated to other molecules.

 

1. Higher copper levels in mice reduced plaque formation.

 

Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14187-92. Epub 2003 Nov 14.
Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Bayer TA, Schäfer S, Simons A, Kemmling A, Kamer T, Tepest R, Eckert A, Schüssel K, Eikenberg O, Sturchler-Pierrat C, Abramowski D, Staufenbiel M, Multhaup G. Department of Psychiatry, Division of Neurobiology, University of the Saarland Medical Center, D-66421 Homburg, Germany. thomas.bayer@uniklinik-saarland.de


The Cu-binding beta-amyloid precursor protein (APP), and the amyloid Abeta peptide have been proposed to play a role in physiological metal regulation. There is accumulating evidence of an unbalanced Cu homeostasis with a causative or diagnostic link to Alzheimer's disease. Whereas elevated Cu levels are observed in APP knockout mice, APP overexpression results in reduced Cu in transgenic mouse brain. Moreover, Cu induces a decrease in Abeta levels in APP-transfected cells in vitro. To investigate the influence of bioavailable Cu, transgenic APP23 mice received an oral treatment with Cu-supplemented sucrose-sweetened drinking water (1). Chronic APP overexpression per se reduced superoxide dismutase 1 activity in transgenic mouse brain, which could be restored to normal levels after Cu treatment (2). A significant increase of brain Cu indicated its bioavailability on Cu treatment in APP23 mice, whereas Cu levels remained unaffected in littermate controls (3). Cu treatment lowered endogenous CNS Abeta before a detectable reduction of amyloid plaques. Thus, APP23 mice reveal APP-induced alterations linked to Cu homeostasis, which can be reversed by addition of dietary Cu.

 

2. Again, higher copper levels in mice reduced plaque formation.

 

Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14193-8. Epub 2003 Nov 14.
In vivo reduction of amyloid-beta by a mutant copper transporter.
Phinney AL, Drisaldi B, Schmidt SD, Lugowski S, Coronado V, Liang Y, Horne P, Yang J, Sekoulidis J, Coomaraswamy J, Chishti MA, Cox DW, Mathews PM, Nixon RA, Carlson GA, St George-Hyslop P, Westaway D.
Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2.


Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-beta (Abeta) peptide. To explore this relationship in vivo, toxic-milk (txJ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Abeta deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive txJ mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Abeta levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS Abeta at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide.

 

3. This study found the opposite.

 

Singh I, Sagare AP, Coma M, Perlmutter D, Gelein R, et al. (2013) Low levels of copper disrupt brain amyloid-beta homeostasis by altering its production and clearance. Proc Natl Acad Sci U S A 110: 14771-14776.

 

Biochemical Studies

Copper stopped plaque protein formation.

 

1. Sci Rep. 2013;3:1256. doi: 10.1038/srep01256. Epub 2013 Feb 13.

Copper prevents amyloid-β(1-42) from forming amyloid fibrils under near-physiological conditions in vitro.
Mold M, Ouro-Gnao L, Wieckowski BM, Exley C.

The Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, ST5 5BG, UK.

 

The aggregation and deposition of amyloid-β((1-42) )(Aβ(42)) in the brain is implicated in the aetiology of Alzheimer's disease (AD). While the mechanism underlying its deposition in vivo is unknown its precipitation in vitro is influenced by metal ions. For example, Aβ(42) is known to bind copper, Cu(II), in vitro and binding results in aggregation of the peptide. The biophysical properties of Cu(II)-Aβ(42) aggregates are of significant importance to their putative involvement in the amyloid cascade hypothesis of AD and are currently the subject of strong debate. In particular the question has been raised if sub- and super-stoichiometric concentrations of Cu(II) act in opposing ways in respectively accelerating and preventing amyloid fibril formation by Aβ(42). Herein we have used fluorimetry and transmission electron microscopy to provide unequivocal evidence that under near-physiological conditions both sub- and super-stoichiometric concentrations of Cu(II) prevented the assembly of Aβ(42) into ThT-positive β-sheet rich amyloid fibrils.

 

2. JOURNAL OF ALZHEIMER'S DISEASE, Volume 18, Number 4, December 2009 Pages 811-817Emily House, Matthew Mold, Joanna Collingwood, Alex Baldwin, Steven Goodwin, Christopher Exley
Copper Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid-β42

 

Abstract: The observation of the co-deposition of metals and amyloid-β42 (Aβ42) in brain tissue in Alzheimer’s disease prompted a myriad of investigations into the role played by metals in the precipitation of this peptide. Copper is bound by monomeric Aβ42 and upon precipitation of the copper-peptide complex thereby prevents Aβ42 from adopting a β-sheet secondary structure. Copper is also bound by β-sheet conformers of Aβ42, and herein we have investigated how this interaction affects the conformation of the precipitated peptide. Copper significantly reduced the thioflavin T fluorescence of aged, fibrillar Aβ42 with, for example, a 20-fold excess of the metal resulting in a ca 90% reduction in thioflavin T fluorescence. Transmission electron microscopy showed that copper significantly reduced the quantities of amyloid fibrils while Congo red staining and polarized light demonstrated a copper-induced abolition of apple-green birefringence. Microscopy under cross-polarized light also revealed the first observation of spherulites of Aβ42. The size and appearance of these amyloid structures were found to be very similar to spherulites identified in Alzheimer’s disease tissue. The combined results of these complementary methods strongly suggested that copper abolished the β-sheet secondary structure of pre-formed, aged amyloid fibrils of Aβ42.

 

3. Copper may protect against the presence of β-sheets of Aβ42 in vivo, and its binding by fibrillar Aβ42 could have implications for Alzheimer’s disease therapy. Exley, C. 2006. “Aluminium and Iron, but Neither Copper nor Zinc, Are Key to the Precipitation of Beta-sheets of Abeta_{42} in Senile Plaque Cores inAlzheimer’s Disease.” J Alzheimers Dis 10 (November): 173–7. 17119286.J Alzheimers Dis. 2006 Nov;10(2-3):173-7. Birchall Centre for Inorganic Chemistry and Materials Science, Keele University, Staffordshire, UK. c.exley@chem.keele.ac.uk

 

A number of metals including Fe(II)/Fe(III), Al(III), Zn(II) and Cu(II) are found co-localised with beta-sheets of Abeta_{42} in senile plaque cores in AD brain. We know neither why nor how the co-localisation takes place or, indeed, if it is entirely aberrant or partly protective. There are data from in vitro studies which may begin to explain some of these unanswered questions and in considering these I have summised that Al(III) and Fe(III)/Fe(II) are directly involved in the precipitation of beta-sheets of Abeta_{42} in senile plaque cores whereas the presence of Cu(II) and Zn(II) is adventitious. The co-deposition of Al(III), Fe(III) and beta-sheets of Abeta_{42} could act as a source of reactive oxygen species and begin to explain some of the oxidative damage found in the immediate vicinity of senile plaques. Whether such metal-Abeta_{42} synergisms are an integral part of the aetiology of AD remains to be confirmed.

 

4. Exley, C. 2006. “Aluminium and Iron, but Neither Copper nor Zinc, Are Key to the Precipitation of Beta-sheets of Abeta_{42} in Senile Plaque Cores in Alzheimer’s Disease.” J Alzheimers Dis 10 (November): 173–7. 17119286.Birchall Centre for Inorganic Chemistry and Materials Science, Keele University, Staffordshire, UK. c.exley@chem.keele.ac.uk

 

A number of metals including Fe(II)/Fe(III), Al(III), Zn(II) and Cu(II) are found co-localised with beta-sheets of Abeta_{42} in senile plaque cores in AD brain. We know neither why nor how the co-localisation takes place or, indeed, if it is entirely aberrant or partly protective. There are data from in vitro studies which may begin to explain some of these unanswered questions and in considering these I have summised that Al(III) and Fe(III)/Fe(II) are directly involved in the precipitation of beta-sheets of Abeta_{42} in senile plaque cores whereas the presence of Cu(II) and Zn(II) is adventitious. The co-deposition of Al(III), Fe(III) and beta-sheets of Abeta_{42} could act as a source of reactive oxygen species and begin to explain some of the oxidative damage found in the immediate vicinity of senile plaques. Whether such metal-Abeta_{42} synergisms are an integral part of the aetiology of AD remains to be confirmed.

 

5. J Alzheimers Dis. 2004 Jun;6(3):291-301. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease. House E, Collingwood J, Khan A, Korchazkina O, Berthon G, Exley C.

Birchall Centre for Inorganic Chemistry and Materials Science, Keele University, Staffordshire, UK.

 

Metals are found associated with beta-pleated sheets of Abeta42 in vivo and may be involved in their formation. Metal chelation has been proposed as a therapy for Alzheimer's disease on the basis that it may safely dissolve precipitated Abeta peptides. We have followed fibrillisation of Abeta42 in the presence of an additional metal ion (Al(III), Fe(III), Zn(II), Cu(II)) over a period of 32 weeks and we have investigated the dissolution of these aged peptide aggregates in the presence of both desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA). Abeta42 either alone or in the presence of Al(III) or Fe(III) formed beta-pleated sheets of plaque-like amyloids which were dissolved upon incubation with either chelator. Zn(II) inhibited whilst Cu(II) prevented the formation of beta-pleated sheets of Abeta42 and neither of these influences were affected by incubation of the aged peptide aggregates with either DFO or EDTA. Freshly prepared solutions of Abeta42 either alone or in the presence of added Al(III) or Fe(III) did not form beta-pleated amyloid in the presence of DFO when incubated for up to 8 weeks. EDTA did not prevent beta-pleated amyloid formation in the same treatments and promoted beta-pleated amyloid formation in the presence of either Zn(II) or Cu(II). The presence of significant concentrations of Al(III) and Fe(III) as contaminants of 'Abeta42 only' preparations suggested that both of these metals were involved in either triggering the formation or stabilising the structure of beta-pleated amyloid. If the formation of such amyloid is critical to the aetiology of AD then the chelation of Al(III) and Fe(III) may prove to be a protective mechanism whilst the chelation of Cu(II) and Zn(II) without also chelating Al(III) and Fe(III) might actually exacerbate the condition.

 

6. J Phys Chem B. 2007 Jul 5;111(26):7646-55. Epub 2007 Jun 12.

Mechanism of copper(II) inhibiting Alzheimer's amyloid beta-peptide from aggregation: a molecular dynamics investigation.

Jiao Y, Yang P.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

 

The aggregation of an amyloid beta peptide (Abeta) into fibrils is a key pathological event in Alzheimer's disease (AD). Under certain conditions, Cu2+ markedly inhibits Abeta from aggregation and is considered as a potential factor in the normal brain preventing Abeta from aggregation. The possible mechanism of the inhibitory effect of Cu2+ was investigated for the first time by molecular dynamics (MD) simulations. On the basis of the radial distribution function analysis of the MD data, a novel strategy, the Q function, was proposed to explore the binding sites of Cu2+ by evaluating the coordination priority of atoms in Abeta, and the [6-5-5] tri-ring 4N binding mode of the Cu2+-Abeta complexes was found. The mechanism of the conformational transition of Abeta from the beta conformation to distorted beta conformations, which destabilizes the aggregation of Abeta into fibrils, was also revealed. All the results provide helpful clues for an improved understanding of the role of Cu2+ in the pathogenesis of AD and contribute to the development of an anti-amyloid therapeutic strategy.

 

And this is an alternate view of brain plaques.

 

From Natural News: Brain plaques do not cause Alzheimer's (we've been lied to for 20 years)O ctober 02, 2010 by: David Gutierrez

 

Turning 30 years of established Alzheimer's dogma on its head, researchers are now increasingly rejecting the theory that sticky plaques in the brain are responsible. "The plaque is not the main culprit in terms of toxicity," said Alzheimer's doctor and researcher Scott McGinnis of Harvard Medical School and Brigham and Women's Hospital.
In Alzheimer's disease, the most common form of dementia, patients' mental functions steadily deteriorate, including their memories and ability to care for themselves. Researchers have long believed that this degeneration was caused by sticky brain plaques of a protein known as amyloid beta. Now, they are instead blaming free-floating pieces of amyloid beta known as oligomers.

"If you say Alzheimer's, everyone immediately thinks that it's the plaques that actually cause the disease. That couldn't be further from the truth," said Andrew Dillin of the Salk Institute in California and the Howard Hughes Medical Institute. "The data actually suggest these plaques are a form of protection that the body tries to put on. So this is a sign that your brain was trying to do something very useful and helpful to you, and the remnant was the formation of amyloid plaques." In a recent study, researchers genetically engineered mice that could produce oligomers but could not form plaques. Compared with mice that could produce both, the plaque-free mice did not fare any better. Similarly, drugs designed to prevent the human brain from forming plaques have consistently failed to deliver any improvement in Alzheimer's patients, and have not slowed the progress of the disease. If plaques are actually a bodily defense mechanism as the new theory suggests, such drugs may actually make things worse. "This [plaque] hypothesis is actually completely wrong, and we need a new way to start looking at this disease," said Dillin. "This is actually not a viable therapeutic avenue."
Learn more: http://www.naturalnews.com/029...s.html#ixzz2gONoii1w




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