Found this interesting:
 

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

George J. Brewer

Article first published online: 22 MAR 2012

DOI: 10.1002/biof.1005

Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc

Abstract

Here's much more from the author of the above study, George J. Brewer.  He discusses his copper hypothesis of Alzheimer's disease and responds to arguments that have been raised against it:

Issues Raised Involving the Copper Hypotheses in the Causation of Alzheimer's Disease
http://www.hindawi.com/journals/ijad/2011/537528/

Also see:

The Risks of Copper Toxicity Contributing to Cognitive Decline in the Aging Population and to Alzheimer's Disease
http://www.jacn.org/content/28/3/238.full 

Here's just a very tiny study:

"... ten patients with Alzheimer's disease were given 27 mg of Zinc (as Zinc aspartate) daily. Only two patients failed to show improvement in memory, understanding, communication, and social contact. In one seventy-nine-year-old patient, the response was labeled 'unbelievable' by both medical staff and family."
- Michael T. Murray, N.D., Joseph E. Pizzorno, N.D., Encyclopedia or Natural Medicine, Revised Second Edition 

And also see:

Does Zinc Help the Brain With Memory?
http://www.livestrong.com/article/390781-does-zinc-help-the-brain-with-memory/ 

Adeona's Pharmaceuticals' reaZin zinc tablet, which I think is zinc cysteine, failed to help much in a recent trial.
http://www.thestreet.com/print/story/11083931.html 


Possibly zinc aspartate (mentioned above in that tiny, very successful trial) and other forms of zinc may work better.

At this point I don't know exactly what forms of zinc were used in the other trials that claimed cognitive improvement.

This may be part of it, Onward, as the cysteine transporter is rendered ineffective in Alzheimer's disease due to oxidation.  The other part may be timing.  As your other post pointed out, some researchers believe that copper and zinc contribute to the aggregation of plaques.  While the plaques are aggregating supplementation with zinc may not be advisable.  But when the aggregation slows down, zinc supplementation may help lower levels of homocysteine and increase superoxide dismutase activity both of which would in turn lower levels of peroxynitrites--the true culprit in Alzheimer's disease.  This strategy may be somewhat more effective that trying to chelate the zinc out of the plaques. 

http://www.ncbi.nlm.nih.gov/pubmed/10801964   

Important is also conversion of 5-htp to serotonin which needs:

- vit. C, B6, Zinc, Magnesium.

Serotonin is responsible for many important things like mood and sleep. Serotonin inhibits/controls dopamine and is a component of reaction which creates melatonin.

Lane and Tom(ek), I appreciate your input. 

Lane, here's a recent, relevant comment from George J. Brewer that might be of interest.  It's about his view of the relationship between zinc and the Alzheimer's plaques.  He views inorganic copper as the bad guy, and zinc as the good guy: 

Issues Raised Involving the Copper Hypotheses in the Causation of Alzheimer's Disease

George J. Brewer 

...  One of the hallmarks of AD pathology in the brain is extracellular amyloid plaques [3]. These are polymers of beta amyloid, a polypeptide clipped off the end of the amyloid precursor protein. The amyloid plaques are thought to be toxic to neurons and are thought to be an integral part of the pathogenesis of AD. These plaques are very rich in copper and zinc, and for a time it was thought both elements were involved in plaque formation [4, 5]. However, it now seems likely that copper is required for plaque formation while zinc is simply bound in large amounts to the plaques. Indeed the plaques, representing a sink for zinc, may add harmful depletion of zinc in the brain [6]. It is already known, based on serum zinc levels, that AD patients are zinc deficient [7], and zinc plays important roles in neuronal function. Thus, copper may be incriminated as a toxic agent, while zinc may be protective, and the brain zinc deficient. Copper also contributes to generation of toxic oxygen radicals in interaction with amyloid plaques [8]. These roles make extracellular copper a potential culprit in the pathogenesis of AD...

[Here are the relevant footnotes:]
 

3. W. Mally and P. Caldwell, Alzheimer's Disease, Key Porter Books, Toronto, Canada, 1998.
 

4. C. S. Atwood, R. D. Moir, X. Huang et al., “Dramatic aggregation of alzheimer by Cu(II) is induced by conditions representing physiological acidosis,” Journal of Biological Chemistry, vol. 273, no. 21, pp. 12817–12826, 1998. View at Publisher · View at Google Scholar · View at Scopus 
 

5. A. I. Bush, W. H. Pettingell, G. Multhaup et al., “Rapid induction of Alzheimer Aβ amyloid formation by zinc,” Science, vol. 265, no. 5177, pp. 1464–1467, 1994. View at Scopus 
 

6. P. A. Adlard, L. Bica, A. R. White, et al., “Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease,” PLoS ONE, vol. 6, no. 3, article e17669, 2011.  
 

7. G. J. Brewer, S. H. Kanzer, E. A. Zimmerman et al., “Subclinical zinc deficiency in Alzheimer's disease and Parkinson's disease,” American Journal of Alzheimer's Disease and other Dementias, vol. 25, no. 7, pp. 572–575, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus 
 

8. D. Religa, D. Strozyk, R. A. Cherny et al., “Elevated cortical zinc in Alzheimer disease,” Neurology, vol. 67, no. 1, pp. 69–75, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus 

Much more here:  http://www.hindawi.com/journals/ijad/2011/537528/ 

Here's another interesting quote from George J. Brewer.  It's important, I think, to note that he thinks the villain isn't "organic copper" (copper in food), but rather the villain is "inorganic copper" (copper in drinking water and in nutritional supplements).  

Here's the quote: 

_________________________________ 

 We have come up with a hypothesis for a plausible, potentially preventable, cause [of Alzheimer's Disease], namely, ingestion of inorganic copper.

We do not claim this as a sole cause, but rather it, along with a high fat diet, sets the stage for the disease to develop, particularly if other risk factors are present.
  

What do we mean by inorganic copper?

We differentiate what we call organic copper, which is copper in food, and which is bound up in organic protein molecules, from simple salts of copper not bound to anything.

The latter, inorganic copper, is the kind of copper present in drinking water and in copper supplements present in most available vitamin/mineral supplement pills.

Since there is almost no protein in uncontaminated drinking water, copper leached off copper plumbing pipes will combine with the cations found in drinking water, such as sulfates, carbonates, and phosphates, to form copper sulfate, copper carbonate, and copper phosphate.

Copper added to vitamin/mineral supplement pills is also a simple salt, often copper sulfate.

As I will discuss, I believe inorganic copper, at least in part, is handled differently by the body than organic copper, and ends up in different places...

Much more here: http://www.hindawi.com/journals/ijad/2011/537528/ 

Dietary supplementation with zinc sulphate, sodium selenite and fatty acids in early dementia of Alzheimer's type.

Abstract

The effect in early Alzheimer's disease of dietary supplementation with compounds containing zinc and selenium, and with fatty acids was studied. 36 subjects (≥60 years old) with early dementia of Alzheimer's type were randomly allocated to evening primrose oil/Zn/Se (EPO/Zn/Se) or olive oil treatment and 30 (15 on each treatment) completed the study. Olive oil, originally intended as a placebo, appeared to have some beneficial effect but significant improvements occurred mainly in the EPO/Zn/Se group. This group showed improved performance on the Anomalous Sentences Repetition Test (P>0.005), the Coloured Progressive Matrices (P<0.005), the Graded Naming Test (P<0.005) and the Digit Copying Test (P<0.01). The improvement in the active group may reflect improved mood (P<0.005) and therefore greater alertness, interest and cooperation with the testing.

http://www.cabdirect.org/abstracts/19911431348.html;jsessionid=A71E9027D61BD6AE6F392F7C54A8B4D7 

Article first published online: 5 OCT 2004

DOI: 10.1002/ddr.430270102 

Thanks, Onward, for the latest research implicating inorganic copper as playing a role in amyloid plaque formation and Alzheimer's disease, and not zinc, which may instead play a protective role.   

I never thought of copper released into water via copper pipes as a potential risk factor for Alzheimer's disease, but I now see that as a possibility.  If so that makes at least three compounds/elements in water that can potentially trigger Alzheimer's disease: inorganic copper, mercury, and aluminium fluoride. 

I think the primary role of zinc in protecting neurons is by lowering homocysteine levels (and thus peroxynitrite levels), but there may well be other mechanisms involved as well.  Polyunsaturated fatty acids may inhibit the activity of the enzymes that trigger Alzheimer's disease: phospholipase C beta and gamma.  Selenoproteins can scavenge peroxynitrites.   

http://www.ncbi.nlm.nih.gov/pubmed/12676458 

This may explain the results from the Rhijn study. 

 


Another article of interest:

http://www.upi.com/Health_News/2012/03/29/Alzheimers-memory-loss-linked-to-zinc/UPI-32741333058775/ 

I've been trying to find studies on zinc for cognitive function and/or dementia, to see exactly what kinds of zinc were used, what dosage, and the outcome.  (Admittedly, some of these studies had just a very small number of participants.)  


_____________________________________________



Adeona's Pharmaceuticals' reaZin zinc tablet, which I think is ZINC CYSTEINE, is said to have failed to help much in a recent trial.
http://www.thestreet.com/print/story/11083931.html 


________________________________________________


For dementia, 220 milligrams of ZINC SULFATE (containing 50 milligrams of elemental zinc) has been used by mouth three times daily for 24 weeks.

http://www.mayoclinic.com/health/zinc/NS_patient-zinc/DSECTION=dosing
[Note: I wish I could locate this study to see the outcome.]


_________________________________________________


Cognitive performance was temporarily improved after 3 months of zinc supplementation (ZINC CHELATE 15 mg) taken twice daily by six subjects with Alzheimer’s disease. Although the initial improvement was not maintained in this small open study, a modest cognitive improvement on psychometric testing was observed at 12 months for the four patients evaluated.
http://medicinalplants.us/zinc-other-uses


_________________________________________________

October 1, 2012 05:21 PM

A new study has outlined for the first time a biological mechanism by which zinc deficiency can develop with age, leading to a decline of the immune system and increased inflammation associated with many health problems, including cancer, heart disease, autoimmune disease and diabetes.


The research was done by scientists in the Linus Pauling Institute at Oregon State University and the OSU College of Public Health and Human Sciences. It suggests that it's especially important for elderly people to get adequate dietary intake of zinc, since they may need more of it at this life stage when their ability to absorb it is declining.
 

About 40 percent of elderly Americans and as many as two billion people around the world have diets that are deficient in this important, but often underappreciated micronutrient, experts say.
 

The study was published in the Journal of Nutritional Biochemistry, based on findings with laboratory animals. It found that zinc transporters were significantly dysregulated in old animals. They showed signs of zinc deficiency and had an enhanced inflammatory response even though their diet supposedly contained adequate amounts of zinc.
 

When the animals were given about 10 times their dietary requirement for zinc, the biomarkers of inflammation were restored to those of young animals.
 

"The elderly are the fastest growing population in the U.S. and are highly vulnerable to zinc deficiency," said Emily Ho, an LPI principal investigator. "They don't consume enough of this nutrient and don't absorb it very well."
 

"We've previously shown in both animal and human studies that zinc deficiency can cause DNA damage, and this new work shows how it can help lead to systemic inflammation," Ho said.
 

"Some inflammation is normal, a part of immune defense, wound healing and other functions," she said. "But in excess, it's been associated with almost every degenerative disease you can think of, including cancer and heart disease. It appears to be a significant factor in the diseases that most people die from."
 

As a result of this and what is now know about zinc absorption in the elderly, Ho said that she would recommend all senior citizens take a dietary supplement that includes the full RDA for zinc, which is 11 milligrams a day for men and 8 milligrams for women. Zinc can be obtained in the diet from seafood and meats, but it's more difficult to absorb from grains and vegetables – a particular concern for vegetarians.
 

"We found that the mechanisms to transport zinc are disrupted by age-related epigenetic changes," said Carmen Wong, an OSU research associate and co-author of this study. "This can cause an increase in DNA methylation and histone modifications that are related to disease processes, especially cancer. Immune system cells are also particularly vulnerable to zinc deficiency."
 

Research at OSU and elsewhere has shown that zinc is essential to protect against oxidative stress and help repair DNA damage. In zinc deficiency, the risk of which has been shown to increase with age, the body's ability to repair genetic damage may be decreasing even as the amount of damage is going up.
 

Medical tests to determine zinc deficiency are rarely done, scientists say, and are not particularly accurate even if they are done. The best approach is to assure adequate intake of the nutrient through diet or supplements, they said, especially in the elderly
.

Even though elderly people have less success in absorbing zinc, the official RDA for them is the same as in younger adults. That issue should be examined more closely, Ho said.
 

Levels of zinc intake above 40 milligrams per day should be avoided, researchers said, because at very high levels they can interfere with absorption of other necessary nutrients, including iron and copper.

http://www.biologynews.net/archives/2012/10/01/zinc_deficiency_mechanism_linked_to_aging_multiple_diseases.html 

"... Preliminary research had suggested that people with Alzheimer's disease should avoid zinc supplements. More recently, preliminary evidence in four patients actually showed improved mental function with zinc supplementation.15 In a convincing review of zinc/Alzheimer’s disease research, perhaps the most respected zinc researcher in the world concluded that zinc does not cause or exacerbate Alzheimer’s disease symptoms.16..."  

Footnotes:

15. Potocnik FCV, van Rensburg SJ, Park C, et al. Zinc and platelet membrane microviscosity in Alzheimer’s disease. S Afr Med J 1997;87:1116–9.

16. Prasad AS. Zinc in human health: an update. J Trace Elem Exp Med 1998;11:63–87.

http://www.truestarhealth.com/Notes/2934002.html 

_____________________________________________

 

Zinc and platelet membrane microviscosity in Alzheimer's disease. The in vivo effect of zinc on platelet membranes and cognition

http://scholar.sun.ac.za/handle/10019.1/7217 

_____________________________________________

Text file of the above study is available at
http://scholar.sun.ac.za/bitstream/handle/10019.1/7217/potocnik_zinc_1997.pdf.txt?sequence=2
It appears to be a scanned document with many typos.  I tried to decipher it below:


Recent years have led to the discovery of several genetic
components implicated in the aetiology of Alzheimer's
disease (AD).' Environmental factors, however, are believed
to accelerate disease expression in genetically susceptible
individuals, as is evidenced by the fact that in monozygotic
twins, age of onset of AD may differ by as much as 15
years, or that the twins may even be discordant for the
disease.

This contrasts with Huntington's disease, in which
no discordancy has been reported. The discovery of
environmental factors responsible for AD in vulnerable
individuals and protection against them could conceivably
alter the date of onset, severity and course of the disease.

A delay in the onset of AD by only 5 years would halve the
prevalence of the illness, resulting in enormous cost-savings
and preventing much human misery.

Atthough AD is seen as a disease of the brain, there is
mounting evidence that peripheral cells are also affected.
In 1987 Zubenko et al. discovered reduced platelet
membrane microviscosity (reciprocal of membrane fluidity) in
55% of AD patients, as well as 8% of healthy control
subjects.

Because this abnormality in platelet membrane
microviscosity occurred in only half of all AD patients, it could
not be used as a diagnostic marker for AD. The observation
that a small proportion of healthy control subjects as well as
some healthy first degree relatives had lowered platelet
membranemicroviscosity has led to speculation about the
susceptibility of these individuals to AD in later life. A long
tenn prospective study, however, would be required to
establish whether this is indeed the case.

Other authors have confirmed the presence of decreased
platelet membrane microviscosity in AD patients.
It has recently come to light that free radical-derived lipid
peroxidation decreases platelet membrane microviscosity,
and that high levels of ascorbic acid eliminate the
membrane damage in the in vitro system.

Zinc also decreases lipid peroxidation in vitro. Jeandel et al. found
that the blood concentrations of several free-radical
scavengers that protect against free radical damage,
including ascorbate and zinc, were significantly lower in AD
patients than in control subjects.

Metal ions alter platelet membrane microviscosity by
binding to charged headgroups of membrane
phospholipids.

Van Rensburg et al. demonstrated that
aluminium ions decreased while zinc ions increased the
microviscosity of platelet membranes in vitro.
A role for zinc in dementia is suggested by the fact that
reduced levels of zinc are found in both plasma and brain
tissue of AD patients, especially in the hippocampus.

The highest concentration of zinc in the brain is found in the
hippocampal mossy fibres, localised in excitatory boutons,
where zinc is co-released with glutamate during neuronal
activity in the form of dense synaptic vesicles.

Westbrook and Mayer suggested that zinc may regulate both excitatory
and inhibitory synaptic transmission in the hippocampus and
that zinc may therefore play an important role in long-term
potentiation,  in the processing of memory formation.

In 1992 a hypothesis was put forward that zinc deficiency
in the hippocampus may contribute to the pathogenesis of
neurofibrillary tangles and that this may be prevented by
treatment with zinc compounds.

Recently, Bush et al. contested this line of thinking by postulating that zinc
actually contributed to AD by precipitating amyloid.This
experiment essentially consisted of adding zinc to a-amyloid
in a test tube and finding the latter aggregated.

While Mantyh et al. showed that aluminium and iron, as
well as zinc, in high concentrations were capable of
aggregating a-amyloid, Bush et al. also reported a negative
effect of zinc on the cognition of a small sample (the number
of patients and the dosage of zinc administered were not
published) of AD patients within a few days of starting
supplementation.'

These findings did not concur with the
results of our own work in progress at the time.

An open-labelled study was undertaken to investigate the
in vivo effects of oral zinc supplementation on: (I) plasma zinc
concentration; (iI) platelet membrane microviscosity; and (iil)
cognitive function of AD patients over a l-year period.

Patients and methods
Six patients (4 men and 2 women; mean age 63.6 years,
range 51 - 79) were diagnosed with AD according to the
definition given by the National Institute of Neurological and
Communicative Disorders and Stroke - Alzheimer's Disease
and Related Disorders Association (NINCDS-ADRDA) work
group and the criteria in the DSM-II/-R,20 as described
previously.

The mean Mini-Mental State Examination
(MMSE score for the patients before supplementation was
16 out of 30 (range 12 - 21). The study was approved by the
Ethics Committee of the University of Stellenbosch.

The 6 AD patients were given oral zinc in the form of ZINC
CHELATED WITH METHIONINE (15 mg twice daily).

Plasma zinc levels and platelet membrane microviscosity were measured
before, during and after the supplementation period. The
patients acted as their own controls.

Plasma zinc levels were determined with a Varian Techtron
Model 1200 atomic absorption spectrophotometer. Platelet
membranes were isolated, and membrane microviscosity
(reciprocal of membrane flUidity) was determined by the
method of Zubenko et al.

The cognitive functioning of 4 AD patients (2 men and 2
women; mean age 67.7 years, range 63 - 72; mean MMSE
18, range 14 - 21) was monitored over a l-year period by
the quarterly administration of a psychometric test battery
which included the MMSE and the cognitive portion of the
Alzheimer's Disease Assessment Scale (ADAS-eog). These
patients were receiving oral zinc chelated with methionine
(15 mg twice daily).

Results

In spite of oral zinc supplementation, the resulting plasma
zinc levels were variable, and even decreased in 2 instances
(Table I). Normal plasma zinc values range between 14 and
34...

In all 6 patients, the platelet membrane microviscosity
values increased to reach similar values within 1 - 3 months
(Patients A - F; Fig. 1). For the group, the increase was
statistically significant (P = 0.02; Wilcoxon rank test).
Increased platelet membrane microviscosity values were
sustained, provided zinc supplementation continued (results
not shown).

Following the initiation of zinc supplementation, all 4
patients showed a modest temporary peak in psychometric
performance at the 3-month mark, relative to their baseline
test scores on the same battery.

This cognitive improvement
coincided with the caregivers' reports of improved day-to
day functioning and was also reflected in the MMSE scores
(Fig. 2). For the MMSE, the highest score is 30...

... For the MMSE, the expected decline is
2.4 • 3 points per year.

... The MMSE decline for the 4 AD patients
after 1 year of zinc supplementation was less than expected

For the ADAS-eog, the perfect score is 0, and in AD an
increase of some 7 - 9 points per year is to be expected.
Again, the decline in cognition of the 4 AD patients after
1 year of zinc supplementation was less than expected

... At the described dosages of zinc
supplementation, all our patients were cognitively better off
after 1 year than if they had not taken zinc.

These results
are in agreement with those obtained by Van Rhijn et al.,
who showed that 15 AD patients receiving dietary
supplementation of zinc sulphate, sodium selenite and fatty
acids over a 20-week period showed significantly improved
performance on psychometric testing. 

The negative effect
observed by Bush et al. in his AD patients within a few days
of zinc supplementation (dosage not pUblished) may have
been due to aluminium, rather than zinc. As a general
principle, an addition of one metal to the body leads to the
redistribution of other metals. linc has been shown to cause
the release of aluminium from membranes and, as
demonstrated previously, aluminium in this free form would
have negative effects on several systems in the body,
causing nuclear damage and alteration of neurotransmitter
and enzyme functions.

Higher levels of zinc would compound this effect.
Furthermore, the very high levels of zinc found in the
hippocampus are enclosed in protective membranous
vesicles. In vitro experiments would not account for this.
In 2 of the 6 patients receiving zinc supplementation, an
increase in libido occurred, necessitating the prescription of
cyproterone acetate. A rise in libido following zinc
supplementation has previously been noted in the
literature.


Discussion

Zinc supplementation unexpectedly did not result in higher
plasma zinc levels in all patients. The variable plasma zinc
levels found may have reflected either a defect in the
absorption of zinc (unlikely, see below) or immediate
redistribution of absorbed zinc into body stores.

The 6 AD patients who received oral zinc supplementation
displayed a steady increase in platelet membrane
microviscosity. This suggests that zinc plays an important
role in maintaining the patency of the microviscosity of
membranes in the body. This role could bestructural, in
that zinc may bind to the charged headgroups of
phospholipids in membranes, or produce an atteration of
the phospholipid composition of the membranes. Driscoll
andBettge found that dietary zinc deficiency in rats
caused a change in erythrocyte phospholipid composition.

Zinc may also protect platelet membranes from decreased
membrane microviscosity caused by lipid peroxidation,8
through the inhibition of free radical reactions.

The fact that oral zinc supplementation had a positive
effect on platelet membrane microviscosity in the presence
of variable plasma zinc levels, indicates that the latter does
not reflect the zinc concentration present in these
membranes.

Though preliminary, the results counter the claims made
by Bush et al. that zinc adversely affects... cognition...

Conclusion

Zinc supplementation corrected the membrane
microviscosity of platelets in a sample of 6 AD patients.
A further ongoing study of 4 patients showed that zinc
supplementation resulted in a modest temporary
improvement in the cognition of all of these patients, as
observed on psychometric testing. This is at variance with
Bush et al.'s report of rapid cognitive deterioration in AD
patients receiving zinc supplementation. The latter effect
may have been dose-related, thus altering the distribution of
and upsetting the balance of other metals in the body, with
negative consequences. We feel that it may be premature to
single out zinc as a causal agent in AD.


 

A few thoughts--some of which may be wrong.  Even if zinc does not play a role in the aggregation of amyloid plaques (which looks more and more likely), if it is absorbed by the plaques anyway then zinc supplementation may not work while the plaques are aggregating.  The enzyme that triggers the aggregation of plaques---phospholipase C--may trigger the export of zinc (further leading to zinc deficiency) and this extracellular zinc may in turn increase phospholipase C activity.  If this is the case, zinc supplementation during the early stages of Alzheimer's disease may be a problem. 

http://www.ncbi.nlm.nih.gov/pubmed/16327063 (the authors of this article argue that at least in certain cells zinc does not increase phospholipase C activity). 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43811/ (the role of phospholipase C in the formation of amyloid plaques). 

Once phospholipase C activity slows down and thus the aggregation of plaques slows down, zinc supplementation may be helpful--because zinc inhibits the further formation of peroxynitrites (the toxin that likely causes Alzheimer's disease).  It does so by lowering homocysteine levels and by increasing superoxide dismutase activity--the zinc-copper driven enzyme that converts superoxide anions into hydrogen peroxide (superoxide anions combine with inducible nitric oxide to form peroxynitrites). 

I hate it when studies seem to produce contradictory results.  This is just one possible explanation around the apparent contradiction--zinc may be harmful or neutral early on and helpful later on. 

Hi, Lane.  Thanks as always for the input.  Ah, if only we had definitive answers for all these things... Obviously much more research is needed.

The following is purely anecdotal, I know, but I still found it interesting in light of the sometimes encouraging results in studies cited in earlier posts.  It's very intriguing to think that zinc supplementation just might help significantly in some cases, even though not in all cases:
See:  http://alzheimersweekly.com/content/zinc-supplement



 

Came across this article advocating zinc therapy:

 

 Thanks, Lane.  Obviously I don't know either.  Interesting, though, that the Van Rhijn study was done specifically on early-stage Alzheimer's patients.  Of course that study involved more than just zinc supplementation though.

Dietary supplementation with zinc sulphate, sodium selenite and fatty acids in early dementia of Alzheimer's type.
http://www.cabdirect.org/abstracts/19911431348.html;jsessionid=A71E9027D61BD6AE6F392F7C54A8B4D7

The article that you cited above, Onward, suggests that zinc can help memory by activating ERK.  This study suggests the same for sodium selenite. 

http://www.ncbi.nlm.nih.gov/pubmed/18547722 

The following study suggests that ERK activation may be detrimental as the disease progresses.   

http://www.ncbi.nlm.nih.gov/pubmed/10439473 

On the other hand, zinc may lower homocysteine levels which would be helpful as the disease progresses.  Long-term studies are needed to answer the question of whether zinc supplementation would be useful or not at different stages of the disease. 

Thanks for finding that, Lane.  Interesting that zinc can activate ERK.  Flavonoids, which have been found to reduce rates of cognitive decline, activate ERK.  Polyphenols also activate ERK.

So I'm guessing that flavonoids and polyphenols (and zinc?) are performing very complex roles that may possibly offset the possible negatives of ERK activation?  I don't know.


 

Yes, it is aggravatingly complicated at times.  I knew some biology before I began studying this disease, but knew nothing about the pathways that may lead to Alzheimer's disease.  You are right there with me Onward, just reading study after study trying to make what sense we can out of them. 

The critical substrate in Alzheimer's disease  is called phosphatidyinositol 4,5 biphosphate.  When it is acted upon by phosphatidylinositol 3 kinase it leads to Akt/Protein kinase B.  This pathway largely helps to protect against Alzheimer's disease (presenilin gene mutations, the APOE4 gene, and bisphosphonate osteoporosis drugs inhibit this pathway to varying degrees). When phosphatidylinositol 3,4 biphosphate is acted upon by phospholipase C (gamma or beta) it leads to intracellular calcium release and Protein kinase C which is the trigger for amyloid plaques, peroxynitrites, and Alzheimer's disease.   

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43811/ 

http://www.ncbi.nlm.nih.gov/pubmed/21708260 

Zinc activates the PI3 kinase/Akt, perhaps through presenilins or perhaps through the activation of the insulin-like growth factor receptor.   

http://www.ncbi.nlm.nih.gov/pubmed/19525380 

The big unanswered question, though, is whether, zinc activates phopholipase C. 

Flavonoids inhibit phospholipase C and thus protein kinase C, and through different means can either inhibit or activate the PI3 kinase/Akt.

http://www.ncbi.nlm.nih.gov/pubmed/10211581 

http://www.ncbi.nlm.nih.gov/pubmed/9225612 

As the article you posted suggests, it is not only the fact that flavonoids are antioxidants, they inhibit one of the key enzymes that lead to Alzheimer's disease (phospholipase C gamma).  And omega 3-fatty acids inhibit the activity of both forms of phospholipase C.  The combination of phenolic compounds (including flavonoids) and Omega 3-fatty acids provide a good combination to delay the onset of Alzheimer's disease.   

http://www.ncbi.nlm.nih.gov/pubmed/16266772 

It appears that zinc in the hippocampus does increase intracellular calcium release via a g-protein coupled receptor (which activates phospholipase C beta) so this might account for the negative studies regarding zinc and memory in Alzheimer's disease. 

http://www.jneurosci.org/content/29/9/2890.short 

Zinc also appears to help activate the phosphatidylinositol 3 kinase/Akt which would explain the positive studies in regards to zinc and memory in Alzheimer's disease. 

More definitive studies are needed.  Zinc supplementation once the above pathways are cut off should have a positive influence. 

Lane and onward,

Thank you so much for all the good information and studies you have posted. I have reviewed much of the Copper and Zinc-related research and would like to get your thoughts on the following observation.

Concerning G. Brewer's excess inorganic Copper hypothesis (http://onlinelibrary.wiley.com/doi/10.1002/biof.1005/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false), he states: "Alzheimer's disease (AD) has become an epidemic in developed, but not undeveloped, countries and that the epidemic is a new disease phenomenon, beginning in the early 1900s and exploding in the last 50 years."

Rapamycin has been shown to inhibit the mTOR pathway which upregulates Autophagy and has been shown to work in mouse models (http://www.eurekalert.org/pub_releases/2010-04/uoth-adt040110.php). I believe the dysregulation of Autophagy is a key factor in AD pathogenisis, and it's interesting that fasting is also known to inhibit the mTOR pathway. Would it not follow Brewer's basic philosophy that fasting is virtually nonexistant in the developed world but common in the undeveloped world. Even the poor don't miss meals in this country and the constant intake of nutrients is part of the signaling pathway for the upregulation of mTOR which in turn inhibits Autophagy.

I would like to draw some connections and find some commonalities with potential environmental causes that are supported by detailed biological research. This may lead us to a workable strategy that involves a combination of readily accessible teatments: Zinc supplimentation, fasting, diet, or even Rapamycin, Bexatotene, Leukine, IgIV, etc.

Serenoa, I'm sorry that I don't understand the science well enough to comment.  But maybe others here, such as Lane, can shed more light.

Thanks for your post.  I'll be interested to hear more, especially about potential treatments, as you pursue this. 

All your posts have been very informative onward. The science is over my head too, but I have learned a lot over the past two years. It seems to me that us novices are going to have to put the clues together ourselves and come up with solutions. There is a huge gap between the researchers and the doctors.

My mother tried Leukine a year and a half ago, six weeks of treatments. There seemed to be improvement in her condition, but it is expensive and others haven't seen the same results. So I continue to search for something better.

Serenoa, thanks.  I appreciate your tenacity and optimism and look forward to more posts from you.  It helps as we share what we find and what we think.  I know I've learned a lot through others who post here.  Am curious to know if you've seen positive results from anything else, other than the Leukine, that you've tried. 

Welcome, Serenoa.  I agree that many people on this board are helping to provide keen insights into the potential treatment of Alzheimer's disease.   

I believe the reason for the low levels of Alzheimer's disease in many developing countries can largely be explained by diets which feature spices, herbs, teas, vegetables, and fruits and a reduced exposure to industrial toxins (such as copper, aluminium fluoride, and mercury).  This may also help to partially explain why in developing countries the rates are lower in rural areas than in urban areas.  In developed countries, places where a Mediterranean diet is adhered too or where there is high consumption of fish, green tea, rice bran, etc. (such as Japan) also have lower incidences of Alzheimer's disease. 

The principal action of rapamcyin in terms of potentially helping against Alzheimer's dsiease is likely through the inhibition of Protein kinase C, which leads to the formation of peroxynitrites--a principal oxidant in Alzheimer's disease.  Bexarotene may also inhibit the formation of peroxynitrites.  Leukine and intravenous immunoglobulin are designed to lower plaque levels which should also lessen peroxynitrite formation. 

Phenolic compounds in various fruits, vegetables, spices, teas, and essential oils and polyunsaturated fats such as fish oil also inhibit the formation of peroxnitrites. Potentially, they may help delay the onset of Alzheimer's disease. 

http://www.ncbi.nlm.nih.gov/pubmed/16266772 

Methoxyphenols are likely the best compounds for treating the disease.  They are effective peroxynitrites scavengers and partially repair the damage that peroxynitrites do to critical transport systems, enzymes, and receptors in the brain.  Eugenol in rosemary essential oil via aromatherapy and coumaric acid, ferulic acid, syringic acid, and vanillic acid in heat-processed ginseng are examples of methoxyphenols that have led to significant improvements in cognitive function in Alzheimer's patients in small-scale clinical trials. 

http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8301.2009.00299.x/full 

http://www.ncbi.nlm.nih.gov/pubmed/22780999 

Inhibit the formation of peroxynitrites and you can delay the onset of Alzheimer's disease; scavenge and partially reverse the damage done by peroxynitrites and you can treat Alzheimer's disease.