RSS Feed Print
Zinc Deficiency and Alzheimer's
Posted: Friday, June 28, 2013 8:55 AM
Joined: 4/24/2012
Posts: 484

Could zinc supplementation help Alzheimer's by regulating the immune system? I had discounted the importance of zinc as it related to the copper toxicity hypothesis, but now I'm seeing some evidence that zinc deficiency causes activation of immune cells in a way that produces oxidative damage. Zinc may be tied up by beta-amyloid in the brain thus causing deficiency and more damage. One study shows that zinc causes the formation of plaques. I am searching for more evidence of a connection between GM-CSF, G-CSF, M-CSF and zinc in the beneficial regulation or promotion of immune response. Zinc is a whole lot cheaper than GM-CSF! But it seems to simple and easy a solution for fixing the immune system aspect of Alzheimer's.


Here's a few studies if found:


Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease



Subclinical zinc deficiency in Alzheimer's disease and Parkinson's disease


Controversial Alzheimer's Disease Risk Factors








Lane Simonian
Posted: Friday, June 28, 2013 9:31 AM
Joined: 12/12/2011
Posts: 5161

The role of zinc in Alzheimer's disease is indeed controversial.  Part of the problem is that the enzyme that converts superoxide anions into hydrogen peroxide depends upon copper and zinc.  When copper and zinc are entombed in amyloid plaques, superoxide anions remain unconverted and instead combine with inducible nitric oxide to form peroxynitrites which cause tissue damage and inflammation.  But the results so far with metal chelators for Alzheimer's disease have been disappointing. 


I am not sure if zinc supplementation would help or not.  Onward posted some good information about zinc and Alzheimer's disease a couple of months ago. 

Posted: Friday, June 28, 2013 10:38 AM
Joined: 12/20/2011
Posts: 217

Serenoa and Lane, thanks for your posts.

Here, I dug up a few of the old threads that may have some info that might be of interest regarding zinc.

2012 study: Zinc supplementation improves cognition in Alzheimer's Disease


 WSJ article: "A New Target in Fighting Brain Disease: Metals"


No evidence that MPACs (PBT1 or PBT2) are of benefit in Alzheimer's dementia

Posted: Sunday, June 30, 2013 9:51 PM
Joined: 4/24/2012
Posts: 484

Thanks onward, good info! There does seem to be something to zinc affecting AD pathology. But is zinc deficiency a causal factor? If so, I'm thinking it's because of its link to dysregulation in the immune system or being tied up in plaques and not so much a nutritional lack of zinc in the diet. It is well known that zinc plays an important role in the immune system.


Lane, good point that zinc deficiency may also be related to peroxynitrite production.


Here is evidence that iron, found in abundance in AD brains, is also tied to the immune system and thus may reach toxic levels in the AD brain due to dysregulation of the immune system.


"For some years now a small group of scientists have been pioneering a revolutionary idea; that the vertebrate immune system could have a role in the regulation of iron in the body. Now a study in the journal Immunology

shows that human lymphocytes (white blood cells) actually produce hepcidin, the most important protein in the regulation of iron levels in the body. What was unexpected was the fact that hepcidin affected lymphocyte multiplication, which occurs for example during an infection, showing that the two systems seem to be much more interlinked than even previously imagined."


I also remember a study and a anecdotal account (on the message board) of how young blood restored cognitive function. Connection?



Lane Simonian
Posted: Monday, July 1, 2013 9:51 PM
Joined: 12/12/2011
Posts: 5161

Thank you Onward and Serenoa for your past and present contributions to this topic.  I don't seem much closer to understanding the role of zinc in Alzheimer's disease just that too little or too much of it can contribute to oxidative stress in Alzheimer's disease.  I don't know how much or if zinc supplementation can maintain the right levels of zinc in the brain. 


The liberation of intracellular zinc may be an early problem in Alzheimer's disease. 



Oxidative and nitrosative stress is a common feature in the initiation and propagation of many neurological and neurodegenerative diseases. Although multiple and distinct signaling cascades are involved in the toxicity of various neural cells, increasing evidence suggests that intracellular zinc liberation is an early initiator and trigger for the subsequent cell death pathways. Activation of protein kinase c (PKC) and mitogen-activated protein kinase (MAPK) by intracellularly released zinc not only contributes to the toxicity of neurons, but also to the toxicity of neuroglia, including oligodendrocytes, astrocytes, and microglia. Therefore, maintenance of the intracellular zinc homeostasis and targeting the downstream signaling molecules may provide therapeutic strategies for the treatment of neurological disorders, in which multiple neural cells may be involved and injured under stressful and pathological conditions.



The same author argues that peroxynitrites contributes to the release of zinc.  The researcher makes a couple of critical observations.



SIN-1 is a commonly used peroxynitrite generator, because it can simultaneously generate nitric oxide and superoxide in aerobic conditions.   Administration of SIN-1 (1 m) to rat forebrain neurons in culture caused severe neurotoxicity. 



We found that...a scavenger of superoxide as well as peroxynitrite, completely blocked neurotoxicity induced by a 4 hr exposure to NMDA. 


But the good news about zinc is that it converts superoxides into hydrogen peroxide--thus at certain levels it can contribute to neuroprotection but at other levels it can contribute to neurodegeneration.  The neuroprotective role of zinc decreases as it is absorbed into amyloid plaques and there may also be problems in regards to the transport of zinc, so it is unclear as Serenoa suggested if zinc supplementation would be helpful at this point.