Dear colleague,

It is supposed that redox metals (especially copper and iron) can potentiate amyloid beta toxicity in Alzheimer disease due to their prooxidant properties (including Fenton chemistry). The mechanism is reviewed in a number of articles:

http://pubs.acs.org/doi/abs/10.1021/cr040410w?journalCode=chreay

http://www.sciencedirect.com/science/article/pii/S136759310700018X

http://pubs.acs.org/doi/abs/10.1021/bi990438f

http://www.sciencedirect.com/science/article/pii/S0005273607000387

Protective role of trace elements is still debatable, however, I suppose that selenium may play a certain role in brain tissue protection in AD. It is a component of the active center of a glutathione peroxidase. Hypothetically, decreased levels of selenium are accompanied by deminished GPx activity and/or synthesis. I hope that the link below may be useful for you:

http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.01854.x/full

Also apart from the element its self iron is proposed to be related to AD as hemin cofactor. It was initially shown by Hani Atamna in 2005 and the biophysics of it was detailed recently by S. G. Dey group. See

http://www.pnas.org/content/101/30/11153.abstract

J Alzheimers Dis. 2006 Nov;10(2-3):255-66.

J Am Chem Soc. 2011 Jan 12;133(1):81-7.

Journal of the American Chemical Society 133 (39), 15545-15552

Having worked in the AD area of the field for a few decades now I have developed a good sense of the models that are being used to promote various treatment approaches. I have never subscribed to the amyloid plaque model--as amyloid plaques in the brain are only found where astroglia have been destroyed. My feeling is that amyloid is there as an immunological response, a kind of "minefield" to slow down the loss of more neurons that otherwise would be unprotected. A whole class of meds (cholinesterase inhibitors) that severely weaken immunology and eventually speed the progression of dementias was based on the flawed amyloid model--falling out of favor at breakneck pace now, it seems. The latest fad now is the "shrunken brain" model. Through years of prescription medications, high caffeine intake, dehydraton, essential fatty acid deficiencies, and chronic micronutrient depletions give us shrunken brains. Why not correct the chronic dehydration and other known contributors before we get into theoretical applications of pharmaceuticals?

But, also untreated hearing loss, we find in a just released study from Johns Hopkins, also appears to contribute to the shrinking brain. I have always maintained that most diagnosis of AD without first removing the hearing loss component and correcting for it is not valid diagnosis. For most older adults have hearing loss, and simply stated, need their hearing tested and corrected before we can be sure of the cognitive components. I will have more to add to this topic, but do appreciate the comments of others already given. Once you get back up on your chair from reading what I have said above I hope you will engage with me in conversation on this. The research to my opinion is quite flawed on AD and self-serving to the vested interests. So we will need to "reason together" if we hope to parse out the real issues on AD. Thank you for inviting my comments.

PS My vote goes to Selenium as the mystery element (smile).

Thank you Max,

is that the traces elements light weight such as aluminum, vanadium , titanium, magnisium or others may be involved in Alzheimer 's Disease?

Yes, you are so right, Benamar. Aluminum is particularly troublesome in AD and other dementias, possibly including Lewy bodies. Zinc deficiency is also troubling--see http://jn.nutrition.org/content/137/4/1101.full for a treatment on that topic. The list of heavy metals that cause dementias is quite well established and the effects of specific deficiencies (B-vitamin, selenium, zinc, and essential fatty acids deficiencies are common in some areas).

Elements such as Cu or Fe that can perform Fenton reaction can triggers REDOX reaction and involved negatively in AD, however elements such as Zn and Se have antioxidant effect so if reduced may cause a problem. These suggested trace elements not only involved in AD but also have a pivotal role in other diseases such as cancer or chronic liver diseases. 

Thank you Noha

There's work linking the Cu, Zn with AD !

What do you suggest as a matrix to analyze (whole blood, plasma, ..)?

Abhishek Dey has direct me to an article linking the disease with iron

"Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin" by Hani Atamna in 2005

How iron metabolism is included?

Fe is the essential element in Fenton reaction, working as a co-factor in various REDOX enzymes, while it is highly toxic when it is in excess as it is responsible for ROS and may results in cellular damage 

I have worked before in a similar issue measuring the serum level of Cu, Fe and Zn in children with chronic liver diseases depending on being oxidants or antioxidants factors which may be the same idea you are interesting in your research

Antioxidant molecule can inhibits damagement of other molecules through inhibits its oxidation. During oxidation reactions there are hydrogen or electrons transfer from a substance to an oxidizing agent. Oxidation reaction produces free radicals or reactive oxygen species ROS such as hydroxyl radical or superoxide anion, thus starts chain reactions. Chain reaction occurs in the cell, causes damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this amazing mechanisms by being oxidized themselves, so antioxidants are often reducing agents in nature such as ascorbic acid.

Oxidation, as Noha ably commented, is at heart of much neuronal damage, and becomes a first order protocol in the eradication of anything in the body that causes oxidation, such as unnecessary medications, ongoing (subclinical infections, mostly from the teeth and jaw), acidosis from overprocessed diet, heavy metal toxicity, and unhealed injuries, particuarly in the spine. We find most oxidative stress is manmade in the form over overmedication, dehydration, and egregious substances in the food supply. 

We are in the process of validating the heme hypothesis in animal brain. We are eagerly waiting for either a yes or no. We don't think it is going to be as simple as that though. As Max has correctly pointed out, fibril formation is likely to be a response to the "cause" and the literature seems to have already decided on what it is (without proper diagnosis).

As a chemist I would like to believe that the root cause is a slow reaction which would fit the generally late onset of the disease. However if a rapid progression phase is present, it would imply that the effect of the main cause is the cause of later progression.

It may be worthwhile mapping the statistical occurrence of the disease in different population with lifestyle (e.g. their food habits). While such data are available for cancer, it was difficult getting such data for AD. In most underdeveloped countries such data are not even reported and AD goes undiagnosed in most cases. This severely limits analysis. May be it is an inappropriate comparison but the progression of AD very closely matches the last stage of a mans life as described by Shakespeare in the seven ages of life making it seem like a natural way to die. Thus much of potentially useful data remains unreported.

Another factor that does seem to me may be related to AD is lack of a disciplined life.  A well maintained daily routine may likely ameliorate many of these problems.