In Part I of this article, it was shown that the cause of Alzheimer's disease (AD) is not high cholesterol, contrary to a growing myth — a myth that provides a great service to the producers of cholesterol-lowering drugs, but does very little to increase our understanding about the truth of Alzheimer's Disease.
So what does cause Alzheimer's disease? The truth is that there is more that we do not know than that we do know.
However, there has been a great deal of research on Alzheimer's that has uncovered genetic, dietary, environmental, and lifestyle factors that unquestionably play a role in causing Alzheimer's, and yield some practical steps we can take to protect ourselves from the disease.
Genetics plays a major contributing factor to the cause of Alzheimer's. Yet animal experiments show that the effect of certain AD-related genes can be modified by diet, and some of the most strongly related genes are only found in five percent of Alzheimer's patients.1
There is strong evidence that depletion of the omega-3 fatty acid DHA — found in quality egg yolks, some fish, and
cod liver oil
— is a primary causal factor in Alzheimer's-related pathology, and insulin resistance appears to also play a role, both of which are modifiable through diet.
Since DHA depletion occurs through, and itself also aggravates, a very high rate of oxidation in the brain, this suggests that dietary antioxidants would be helpful in preventing Alzheimer's.
Taken together, it appears that eating a diet rich in traditional whole foods of both animal and plant origin, low in vegetable oils and excessive amounts of carbohydrates would strongly protect against Alzheimer's.
Are Genetics the Cause of Alzheimer's?
There are many genes that have been studied in relation to Alzheimer's disease, but there are a few that stand out.
The ApoE4 Allele As the Cause of Alzheimer's
Apolipoprotein E (apoE) is an essential molecule to the brain that is involved in the transport of cholesterol and other lipids. There are several different forms of the gene for apoE, and one of them, epsilon-4,(apoE4) is correlated with Alzheimer's disease.
The epsilon-4 allele of apoE is very common. To date, meta-analysis from the
Alzheimer's Research Forum
shows that it is present in about 13 percent of the population, but 36 percent of the Alzheimer's population.2
Although apoE4 occurs nearly three times as frequently in Alzheimer's populations than in the general population, neither one nor two copies of the allele is either necessary or sufficient to cause Alzheimer's disease.1
Although beta-amyloid aggregation is higher in the presence of the epsilon-4 allele, that is not the end of the story.
When apoE4 is added to neurons in cell culture, isolated from any effects on or of beta-amyloid, it inhibits the growth of axons and dendrites, whereas the other forms of apoE enhance the growth of axons and dendrites, relative to a straight lipoprotein medium.3
Why is this?
First, it is important to understand the significance of apoE in the brain.
In 1997, it was found that some factor in the secretion of glial cells, which grow alongside neurons, was responsible for the ability to form synapses, which are the connections between the axon of one neuron and the dendrites of another. For four years it remained unknown what this mystery "glial factor" was, but in 2001 it was identified as apoE-enriched cholesterol.4
Without the glial secretion, neurons formed few and inefficient synapses. With it, they formed many efficient synapses. The measurements of the unknown factor matched apoE, which is reponsible for transporting cholesterol and other lipids from glial cells to neurons.
But isolated ApoE did not have the effect of the mysterious and elusive "glial factor," nor did some of the non-cholesterol lipids it carried, which even proved toxic to neurons at high doses. Isolated cholesterol, on the other hand, did.
Exposing glial-deprived neurons to a solution of isolated cholesterol increased their synapse formation by twelve times. Producing a cholesterol-free glial secretion with a statin drug abolished the effect of the glial factor.
Thus, apoE's primary benefit to the nervous system appears to be its delivery of cholesterol to neurons, which is necessary for synapse formation.
Dr. Iwo Bohr has suggested that apoE4 is less able to efficiently deliver cholesterol to neurons, and that this characteristic contributes to its causal role in Alzheimer's disease.5
Dr. Bohr cites Lane and Farlow6, who observe that apoE4 is less efficient at transporting free fatty acids, and notes that apoE4 is associated with a higher level of cholesterol, which may indicate that cholesterol is not being internalized into cells efficiently.
Yet a 1998 study by Zhong-Sheng et al.7 appears, at least at first glance, to contradict this.
They compared the effect of apoE3 to that of apoE4 on neuronal cell culture, incubating both forms of apoE in beta- very low-density lipoprotein (beta-VLDL), and found that apoE4 was slighlty more efficient at delivering cholesterol to cells, although apoE3, not its associated cholesterol, was retained within the cell at several times the amount that apoE4 was retained. This appeared to occur because apoE4 was quickly released from the cell, not because it was broken down within the cell.
Even still, apoE3 enhanced dendrite and axon growth, while apoE4 inhibited dendrite and axon growth.
This appears to suggest that while cholesterol is the limiting factor in the formation of synapses, internalized apoE might be the limiting factor in the initial growth of the axons and dendrites. It is unknown why there is a difference between the two forms of apoE in this matter, but there are several (speculative) possibilities:
apoE or one of its breakdown products is needed by the cell to deliver cholesterol to lipid rafts in the membrane, which are known to be necessary signaling molecules involved in the growth of dendrites and axons8 (My suggestion)
apoE is released into the cytosol (the inside of a cell) where it complexes with other proteins necessary for axon and dendrite growth (Suggested by Zhong-Sheng et al.)
It is important to be careful of drawing conclusions from this study. Since this study was in vitro — using isolated cells rather than a living organism — it utilized conditions that would not occur in a living organism. For example, both forms of apoE were only incubated with VLDL, and not other lipoproteins, such as chylomicrons, IDL, LDL, and HDL.
This, in fact, is critical to evaluating the observation of whether or not apoE4 is less or more efficient at delivering cholesterol to cells.
Lane and Farlow note that apoE4 has a preferential affinity to bind to high-triglyceride lipoproteins like chylomicrons and VLDL, as opposed to low-triglyceride lipoproteins such as LDL, IDL, and HDL.6 While they are making a different point, this observation bears an important corollary that has gone unnoticed:
High-triglyceride lipoproteins are also low-cholesterol lipoproteins!
According to Figure 2.10 in Dr. Mary Enig's book,
Know Your Fats,
excluding HDL, there is an inverse relationship between cholesterol and triglyceride percentage of a lipoprotein.9 The following data is derived from this table, but excludes irrelevant information:
As you can see, apoE4, by binding to high-triglyceride lipoproteins, is also preferentially binding to low-cholesterol lipoproteins.
Thus, in a living organism, it appears that apoE4 is less effective than other forms of apoE at delivering cholesterol to cells because it prefers lipoproteins that have less cholesterol.
This is consistent with the observation that cholesterol levels are higher in people bearing the apoE4 allele, possibly due to deficient internalization of that cholesterol, and supports Dr. Bohr's hypothesis.
ApoE4 has other effects as well. It is less efficient at delivering DHA to neurons, the importance to Alzheimer's of which will be discussed below, and which may be related to its association with insulin resistance.6
Is ApoE4 the "cause" of Alzheimer's? As Tanzi and Bertram note,1, even carrying two copies of the allele is not sufficient to cause Alzheimer's, nor is carrying even one copy necessary to cause Alzheimer's. Therefore, there must be dietary and/or environmental (or other genetic) factors that interact with ApoE4's ability to contribute to the cause of Alzheimer's.
Lane and Farlow6 note that apoE4 has many of the same effects as a high-carbohydrate diet, and review evidence showing that apoE4 is least common in populations with a long history of agriculture, and most common in present hunter-gatherer populations, ranging from four percent in Israel to 40.7 percent among African Pygmies.
It may well be that apoE4 is only a harmful gene if it is accompanied by a high-carbohydrate diet that one's ancestors have not partially adapted to by weeding out the apoE4 gene.
APP Mutations as the Cause of Alzheimer's
Since amyloid precursor protein (APP) is the precursor of beta-amyloid, one may intuitively jump to the conclusion that its role in Alzheimer's disease is primarily related to this particular function.
Yet a study, discussed below, by Takahishi et al.10 showed a very different problematic characteristic of a common APP-related mutation.
APP has many roles, and is both secreted from the cell and exists inside the cell. When APP is located inside the cell, it binds to an enzyme called heme oxygenase (HO).
HO protects cells by transporting iron, an oxidizing agent, out of the cells, and is also responsible for the production of bilirubin, which is an antioxidant with neuroprotective effects.
APP695, which is a mutant form of APP associated with familial Alzheimer's disease (FAD), has a significantly greater effect at inhibiting HO than the "regular" form of APP. This provides an explanation for how this mutation could contribute to Alzheimer's in addition to or even despite its relation to beta-amyloid.
As we will see below in the section on DHA, a high oxidation rate in the brain appears to contribute a much greater proportion to the cause of Alzheimer's disease than does the formation of amyloid plaques, through the massive oxidation and depletion of DHA, an essential fatty acid, and the proteins that form synapses. We will also see that harm done through this oxidation can be largely controlled through diet.
Presenilin Mutations as the Cause of Alzheimer's Disease
Presenilins (PS), which include presenilin-1 (PS1) and presenilin-2, (PS2), are important to both the nervous system and the entire body for many different reasons. They also happen to be subunits of the gamma-secretase enzyme, which cleaves APP into beta-amyloid.
Therefore, mutations in the presenilins associated with Alzheimer's disease could be regarded as circumstantial evidence favoring the amyloid hypothesis.
Yet, it turns out that a more in-depth look at the relation of PS1 and PS2 to the neuropathology seen in Alzheimer's disease paints a very different picture.
Research into the possibility of using presenilin-inhibitors as drugs to treat Alzheimer's should be regarded as yet another nail in the coffin of the amyloid hypothesis, which, as Dr. Koudinov has tirelessly pointed out, is being supported by researchers who continually violate institutional standards in failing to disclose information about their conflicting financial interests.11
The amyloid hypothesis would predict that inhibiting presenilins would, in turn, inhibit gamma-secretase — which cleaves APP into beta-amyloid — which would, then, decrease the production of beta-amyloid.
The amyloid hypothesis holds that decreased production will lead to decreased accumulation, and thus decreased formation of amyloid plaques. This would result in a decreased neurofibrillary tangles and the other characteristics of Alzheimer's that are all supposedly caused by beta-amyloid accumulation.
So, drugs that inhibit presenilins should be a prime candidate for Alzheimer's.
Yet a study by Marjaux et al. proved quite otherwise. Knocking out PS1 in mice specifically in the brain led to a decrease in beta-amyloid, along with mild memory impairment.
The absence of both PS1 and PS2 led to "strongly impaired LTP [long-term potentiation, necessary for memory], spatial and contextual memory deficits, and, after some time, massive loss of synapses, dendrites, and neurons. Remarkably, this neurodegeneration was accompanied by increased Tau phosphorylation . . ."12
The increase in tau phosphorylation is "remarkable" because excessive tau phosphorylation is what leads to neurofibrillary tangles. The amyloid hypothesis would have predicted that decreasing beta-amyloid accumulation would decrease the chance of developing tangles, and prevent the neurodegeneration seen above, yet the precise opposite took place.
While this study does not necessarily show a causal role in a deficiency of beta-amyloid for the associated results, it certainly calls deeply into question whether beta-amyloid is the cause of Alzheimer's-related neurodegeneration that occurs in its absence.
However, it also cannot be ruled out that decreasing beta-amyloid was in itself harmful. Dr. Koudinov has reviewed studies showing positive effects of beta-amyloid, and showing that beta-amyloid corrects the neurodegenerative effects of cholesterol deficiency, and that this positive effect is abolished by cholesterol-lowering drugs.13
Since the presenilins have so many important functions, it is likely that PS mutations related to Alzheimer's disease decrease the ability of PS to perform its important functions, which could possibly even include positive effects of beta-amyloid.
The apoE4 allele is the most common among Alzheimer's patients, being present in about 36 percent of cases, yet it is neither sufficient nor necessary to cause Alzheimer's disease.
On the other hand, the mutations in APP, PS1, and PS2 are present in only five percent of AD cases. Although they account for only a small portion of Alzheimer's disease, Tanzi and Bertram regarded them as "fully penetrant" in a recent review, their presence guaranteeing the development of Alzheimer's disease.
Yet this should remain an open question. As will be discussed in the next section, the neurodegeneration in mice with APP mutations can be controlled dietarily. Since deficiencies of DHA and other dietary factors are nearly universal in modern societies due to changes not only in what we eat, but also how that food is produced, studies may be missing important environmental factors that regulate the expression of these genes simply because they are not varied in the populations we study.
Additionally, studies with rodents invariably come to the impossibility of reconciling the standard cereal-based lab chow with the fact that a single wild population of mice or rats that has invented agriculture has yet to be found.
DHA-Depletion as the Cause of Alzheimer's
While the studies reviewed in Part I of this article that fed hypercholesterolemic diets to rodents, one inducing, the other decreasing, amyloid deposits, didn't bother to measure the cognitive function of the rodents, the story is different for DHA. And while the results of cholesterol-feeding have been contradictory, the story is again different for DHA.
Docosohexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid found in such foods as
cod liver oil,
fatty fish, and egg yolks from chickens raised on pasture. Considerable evidence of various kinds indicates that DHA deficiency plays a causal role in Alzheimer's disease.
Low dietary intake of DHA is a risk factor for Alzheimer's disease14, and low serum levels are likewise correlated with occurance of Alzheimer's as well as the degree of progression of dementia.15 Brain levels of DHA in the hippocampus are considerably deficient in patients with Alzheimer's disease.16 Additionally, supplementing with DHA improves memory in the elderly.17
Animal experiments demonstrate conclusively that both the pathological hallmarks of Alzheimer's disease as well as mental functioning can be modified in rodents by modifying dietary intake of DHA.
A 2004 study found that supplementing with DHA reversed the effects of beta-amyloid infusion on memory errors in an 8-arm radial maze. The study inserted an osmotic pump into the brains of these rats to allow a constant infusion of aggregated beta-amyloid to enter the brain in two groups of rats, one with DHA supplementation, the other without. A third group was fed DHA group but not given beta-amyloid infusion, and a fourth, control group had neither DHA supplementation nor beta-amyloid infusion.18
Obviously conclusions from this study must be drawn hesitantly and conservatively, since there is no way to know how closely having an osmotic pump inserted into one's brain with a constant influx of beta-amyloid approximates natural conditions of Alzheimer's. It would have been interesting to have a control of another substance pumped into the brains of rats, to compare to the effect of aggregated beta-amyloid.
Nevertheless, not only did DHA protect from the effects of beta-amyloid infusion, but the DHA brain-pump group performed better on cognitive tests than even the control group!
One interesting point is that the beta-amyloid infusion only had reproducibly negative effects on cognitive impairment when aluminum chloride was added to the infusion, which causes beta-amyloid to aggregate.
Not only is this evidence against the claim of the amyloid hypothes that amyloid plaques are merely the product of accumulation of beta-amyloid, but the fact that aluminum was being infused into the brains of these rats should raise a red flag to anyone eager to blame memory impairments on the beta-amyloid.
Of course, neither the aluminum used nor the fact that non-aggregated beta-amyloid had no reproducible effect were noted in the abstract.
A 2005 study found that dietary DHA decreased the level of insoluble beta-amyloid and amyloid plaques, but did not influence the level of soluble beta-amyloid, and cognitive effects were not measured.19 It is particularly surprising that the authors referred to beta-amyloid as the "causal factor" in Alzheimer's disease when the level of soluble beta-amyloid was not associated with the degree of plaque in this study, and the same group of researchers published a study in 2004 showing DHA to regulate massive dendritic pathology by mechanisms that were independent of beta-amyloid!
The most enlightening animal study of DHA's relation to Alzheimer's was this 2004 study by the above authors.20 In this study, they explicitly state that memory loss has a greater correlation with the degeneration of dendrites than it does with plaques or tangles.
In Alzheimer's disease, there is a 70-95 percent loss of debrin through oxidation, which is a protein that regulates another protein, actin, in the dendritic spine, and a 17 percent loss of another synaptic protein, synaptophysin.
Depleting mice that had a human APP-mutated gene associated with Alzheimer's disease (called "transgenic" mice) of dietary DHA caused an 85% loss of debrin, and a rapid depletion of brain DHA, which makes up 15 percent of the brain and concentrates at synapses.
DHA also caused the cleavage of actin into fractin, which is associated with Alzheimer's pathology. Supplementing the diet restored entirely both the debrin and actin, and restored the brain DHA level.
DHA-depletion also caused learning deficits in the mice with the AD-related gene, as measured in a water maze, which was restored by adding DHA back into the diet. Mice without the AD-related gene did not have such a high depletion rate of brain DHA levels nor the other pathology.
The authors noted that DHA-depletion also caused the loss of a subunit of an enzyme called P13-kinase, which is involved in insulin signaling, the dysfunction of which has been associated with Alzheimer's disease.
Beyond a certain aging point,the transgenic mice began to develop some cognitive defects even when fed DHA. The authors rightly pointed out that it is unknown whether earlier intervention with DHA during development may have had a more profound effect.
It should also have been noted that, in a disease notably related to insulin resistance, to which a cereal-based diet could contribute both through an autoimmune mechanism and through a supply of excessive carbohydrates, similar experiments should be performed that attempt to approximate a diet natural to a wild member of the species.
In any case, it is quite clear from both human and animal studies that DHA-deficiency contributes to at least a portion of the cause of Alzheimer's, and that modifying it dietarily modifies the pathology of Alzheimer's.
Insulin Resistance as the Cause of Alzheimer's Disease
Considerable evidence indicates that insulin resistance plays a role in the development of Alzheimer's disease. Insulin is responsible for bringing glucose into cells, and prolonged, chronic, high levels of insulin can lead to insulin resistance, where insulin is incapable of exerting its effect on cells.
Type 2 diabetes is characterized by insulin resistance. Population studies indicate that Type 2 diabetics have two to three times the risk of Alzheimer's disease as the general population.21, 22
In a commentary in The Lancet, Mark Strachan reviewed research showing that, on the one hand, insulin has a profound effect improving memory, and on the other, high blood levels of insulin are associated with increased memory decline.
This indicates that insulin resistance leads to cognitive dysfunction because of insulin's inability to carry out its proper function.23
It has been hypothesized that high-carbohydrate diets could lead to Alzheimer's disease through chronic over-exposure of cells to insulin signaling, which accellerates cellular damage in cerebral neurons,24 and can cause insulin resistance.25
Indeed, this is highly suggested by the frequency of AD-related genes across different populations. The apoE4 allele, for example, is nearly three times more frequent among Alzheimer's populations than the general population,2 yet this gene appears to be selected against by populations with a long history of high-carbohydrate diets. The following table shows the frequency of the apoE4 allele in various populations, with data supplied by a review by Lane and Farlow.6
Greek 6.8% African Pygmies 40.7%
Turks 7.9% Papuans 36.8%
Mayans 8.9% Inuits 21.4%
Arabs in Northern Israel 4%
As can be seen above, and as pointed out by Lane and Farlow, the lowest frequencies of the apoE4 allele are found in populations with a long history of agriculture, and the highest frequencies are found in long-time hunter-gatherer populations.
High-carbohydrate diets and the apoE4 allele alike share many problematic characteristics including the depression of lipid metabolism.6 It appears that the combination of a high-carbohydrate and the apoE4 allele leads to disastrous health consequences not limited to Alzheimer's.
In consequence, populations with a long history of agriculture have successfully weeded out the gene — through a history of carbohydrate-induced fatal disease — while individuals in modern societies disconnected from the pattern in which their ancestors have traditionally eaten are now succumbing to these diseases because of these dietary factors.
Animal experiments verify a role for insulin resistance as a contributing cause of Alzheimer's disease. A 2004 study found that diet-induced insulin resistance in mice with an AD-related APP mutation caused a decrease in the P13-kinase enzyme, which also occurs under DHA-depletion (discussed earlier), increased amyloid plaque burden, and caused impairment of performance in a water maze. Interestingly, the insulin resistance also caused a relationship to appear between gamma-secretase activity (which forms beta-amyloid) and AD-related pathology, which seems to indicate that it is insulin resistance that might cause beta-amyloid to become harmful.26
Another 2004 study found that mice with the same gene mutation were inherently insulin-resistant,27 at least on the diet they were fed. By eight months the transgenic mice (the mice who contained the human APP mutation) demonstrated poor glucose tolerance, and by thirteen months they became hyperinsulinemic. This result was avoided by a drug that increases insulin sensitivity.
Oddly, the authors of the first study claim to have induced insulin resistance with a high-fat (60 percent), low-carbohydrate (20 percent) diet. This is interesting, because in the second study, insulin resistance developed on the standard diet, which, according to macronutrient data on Dyet Inc.'s website28 is a low-fat (15 percent), high-carb (65 percent) diet.
Additionally, the website of the supplier of the diets in the first study,29 Research Diets Inc., even claims itself that its high-carbohydrate diet is used to induce insulin resistance. The induction of insulin resistance by a high fat diet could be an aberration caused by the particular strain of mice.
Or, it could be a result of the fact that the fats in the diet are processed by extrusion into pellets,30 which is a high-pressure, high-heat process that would cause major damage to the unsaturated fats with toxic byproducts, possibly including trace amounts of trans fats,31 which are known to contribute to insulin resistance.32
Additionally, that apoE4 is seen less often in agricultural societies than hunter-gatherer societies indicates that it is the high-carbohydrate diets made possible by agriculture that are the culprit, rather than high-fat diets. Evidence also suggests that extremely high-fat, ketogenic diets would be beneficial to Alzheimer's.33
It must be emphasized that the healthful alternative to a high-carbohydrate diet that improves insulin sensitivity is not a high-protein diet. A high-protein diet is metabolically similar to a high-carbohydrate diet because nearly half of the amino acids in most protein foods are glucogenic, mean they convert readily to glucose, which is sugar. The healthful alternative is a high-fat diet.33
It has been a great disservice to public understanding that diets such as the Atkins diet are referred to as "high-protein," when such diets, properly done, are high-fat diets. The attempt of many ill-informed consumers to try to do low-carb diets and low-fat diets at the same time has no doubt led to many negative health effects as the result of excessive protein consumption.
Oxidation as a Cause of Alzheimer's Disease
Thus far in this article we've seen that oxidative damage in the brain is a central feature of Alzheimer's disease. For example, the APP695 mutation discussed above decreases anti-oxidant activity in the brain, and DHA-depletion, also discussed above, causes massive oxidation of important synaptic proteins.
As Lane and Farlow point out,6, low intake of antioxidants is a risk factor for Alzheimer's disease,34 one population study found that cholesterol is only a major risk factor for Alzheimer's disease if it is accompanied by high transferrin, which transports iron, an oxidative agent,35 and Alzheimer's disease is characterized by a higher rate of oxidation in the brain.36
Since oxidative damage is determined by:
a low antioxidant status
a high consumption of oxygen
a low capacity for regeneration6
it would be a sensible precaution against Alzheimer's disease to increase antioxidant consumption and to decrease excess consumption of easily oxidized substances. This translates to an increased intake of fresh, unrefined, unprocessed fruits and vegetables, avoiding excessive cooking, which destroys anti-oxidants, and decreasing intake of polyunsaturated fat.
While DHA, a polyunsaturated fat, is protective, it is also true that DHA is only one of many polyunsaturated fats, and that modern diets tend to be deficient in DHA while being enormously excessive in other polyunsaturated fats from vegetable oils.
Polyunsaturated fats contain many double-bonds, which are targets for oxidation, whereas monounsaturated fats contain only one double bond, and saturated fats contain no double bonds.
Therefore, a prudent, anti-oxidative diet should include a high saturated fat to unsaturated fat ratio, and a minimum of polyunsaturated fat, providing it is sufficient in DHA.
Other Causes of Alzheimer's Disease
There is much more to be known about Alzheimer's than we know now. However, research increasingly is implicating other factors in Alzheimer's disease, including the accumulation of toxic metals in the brain and excitotoxicity (the death of neurons by excessive excitation) of glutamate.
These factors also interact with genetics, since apoE is responsible for sequestering heavy metals in the brain as well as protecting against the excitotoxic effect of glutamate, while apoE4 is less efficient at both than other forms of apoE6
However, since both of these factors are highly regulated in the body by complex mechanisms, more research needs to be done to determine exactly what dietary and environmental risks are. Still, it makes sense to take reasonable precautions by avoiding exposure to aluminmum and other heavy metals, and avoiding intake of MSG, a source of excitotoxic glutamate.
Another factor may be engagement in stimulating activity. In a 2002 study reported in the Journal of the American Medical Association, it was found that, after adjusting for age, sex, and education, a 1-point increase on a test of cognitive activity translated to a 33 percent reduction in the risk of Alzheimer's disease.37 This suggests that another protective measure we can take is to simply stay active: read, write, listen to music, and so on.
Although, it seems possible that this could be a reflection of decreased cognitive activity in people predisposed to Alzheimer's. And thus, it becomes a chicken-and-egg problem. Nevertheless, engaging in stimulating activity is clearly a positive thing to do regardless, and could in fact be protective.
Finally, Dr. Kilmer McCully, who did ground-breaking and revolutionary work connecting a protein-derivative, homocysteine, to heart disease, has informed me that there is a growing interest in the relationship between homocysteine and Alzheimer's.
Elevated homocysteine levels are associated with Alzheimer's. Homocysteine levels become elevated through a deficiency of B vitamins, largely a result of modern processing of vegetables and the disappearance of liver from the modern menu.
Conclusions: Causes of Alzheimer's Disease
Even though many are advocating a low-cholesterol, low-fat diet to prevent Alzheimer's, based on the dubious notion that cholesterol causes beta-amyloid accumulation, which, in turn, causes Alzheimer's disease, the use of this deceptive and out-dated model shouldn't prevent us from taking real, science-based precautions against Alzheimer's disease.
It appears highly evident that DHA-depletion, insulin resistance, increased oxidation, and perhaps activity levels and homocysteine levels, are all controllable factors that are partial causes in the development of Alzheimer's disease.
Genetics plays a factor, but genes are clearly only part of the picture. It makes sense to increase our consumption of fresh fruits and vegetables, saturated fats, and sources of DHA such as egg yolks from pastured chickens and cod liver oil, and to decrease our consumption of carbohydrates and most polyunsaturated fatty acids. A high-fat diet may help by preventing insulin resistance and by contributing neuro-protective ketone bodies as well.
Medium-chain triglycerides (MCTs) are also effective in increasing ketone bodies regardless of other dietary factors,33 so the addition of coconut oil to the diet, the best food source of MCTs, might also be a protective factor.
Naturally, avoiding processed foods or cooking materials that contain metals like aluminum and excitotoxins like MSG are also reasonable precautionary measures.
And lastly, staying active appears to protect against Alzheimer's, reminiscent of the old adage, "use it or lose it."
In addition to fish and fish oils, DHA is available from pasture-raised animal products. Since modern supermarkets usually do not contain such beneficial foods, local farms are often the best way to procure them.
will help you find sources of pasture-fed animal products in your area. And our page on
liver and cod liver oil
will assist you in finding the highest quality cod liver oil.
Cholesterol is not the cause of Alzheimer's disease. But, given it's relation to mental performance, a lack of it may contribute to the maintenance of outdated and thoroughly refuted scientific theories.
You can peruse the references, share this article, or leave a comment below.
Read more about the author, Chris Masterjohn, PhD, here.
1. Tanzi, Rudolph E., and Lars Bertram, "Twenty Years of the Alzheimer's Disease Amyloid Hypothesis: A Genetic Perspective," (Review) Cell, Vol. 120, 545-555, February 25, 2005.
2. Bertram L, McQueen M, Mullin K, Blacker D, Tanzi R. The AlzGene Database. Alzheimer Research Forum. Available at: http://www.alzgene.org. Accessed August 4, 2005.
3. Zhong Sheng, et al., "Differential Cellular Accumulation/Retention of Apolipoprotein E Mediated by Cell Surface Heparan Sulfate Proteoglycans," The Journal of Biological Chemistry, Vol. 273, No. 22, Issue of May 29, pp. 13452-13460, 1998.
4. Mauch et al., "CNS Synaptogenesis Promoted by Glia-Derived Cholesterol," Science, Vol. 294, 1354-1357, 2001.
5. Bohr, Iwo J., "Does cholesterol act as a protector of cholinergic projections in Alzheimer's Disease?" Lipids in Health and Disease, 2005, 4:13.
6. Lane and Farlow, "Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease," Journal of Lipid Research, Volume 46, 2005.
7. Zhong-Sheng, et al., "Differential Cellular Accumulation/Retention of Apolipoprotein E Mediated by Cell Surface Heparan Sulfate Proteoglycans," The Journal of Biological Chemistry, Vol. 273, No. 22, Issue of May 29, pp. 13452-13460, 1998.
8. Guirland, et al., "Lipid Rafts Mediate Chemotropic Guidance of Nerve Growth Cones," Neuron, Vol. 42, 51-62, April 8, 2004.
9. Enig, Mary G., PhD, Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils, and Cholesterol, Silver Spring: Bethseda Press, 2000, p. 70F.
10. Takahashi, et al., "Amyloid Precursor Proteins Inhibit Heme Oxygenase Activity and Augment Neurotoxicity in Alzheimer's Disease," Neuron, Vol 28, 461-473.
11. See, for example, Koudinov, "Hasta la vista, amyloid cascade hypothesis, OR will academic dishonesty yield Alzheimer's cure?", letter to Kenneth Blum, Neuron, Cell Press, published online at http://sageke.sciencemag.org/cgi/eletters/pmid;12765607#191. Accessed August 5, 2005.
12. Marjaux, et al., "Presenilins in Memory, Alzheimer's Disease, and Therapy," Neuron, Vol. 42, 189-192, April 22, 2004.
13. Koudinov and Koudinova, "Amyloid Beta Protein Restores Hippocampal Long Term Potentiation: A Central Role for CholesteroL?" Neurobiology of Lipids, Vol. 1 article 8, 2004.
14. Morris, et al., "Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease," Arch Neurol. 60: 940-946, 2003.
15. Tully et al., "Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study," Br J Nutr. 89 (4): 483-9 Apr 2003.
16. Soderberg, et al., "Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease," Lipids 26: 421-425, 1991.
17. Suzuki, et al., "Effect of DHA supplementation on intelligence and visual activity in the elderly," in Fatty Acids and Lipids - New Findings (Hamazaki T. & Okuyama H., eds.) World Rev. Nutr. Diet. 88: 68-71, 2001.
18. Hashimoto et al., "Chronic Administration of Docosahexaenoic Acid Ameliorates the Impairment of Spatial Cognition Learning Ability in Amyloid ß-Infused Rats," Nutritional Neurosciences, Epub November 2004.
19. Lim et al., "A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Buren in an Aged Alzheimer Mouse Model," Journal of Neuroscience, 25(12):3032-3040, March 23, 2005.
20. Calon et al., "Docosohexaenoic Acid Protects from Dendritic Pathology in an Alzheimer's Disease Mouse Model," Neuron, vol 43, 633-645, Sept. 2, 2004.
21. Leibson, et al., "Risk of dementia among persons with diabetes mellitus: a population-based cohort study," Am. J. Epidemiol. 145, 301-308, 1997.
22. Stolk, et al., "Insulin and cognitive function in an elderly population. The Rotterdam Study," Diabetes Care 20, 792-795, 1997.
23. Strachan, Mark W J, "Insulin and Cognitive Function," (Commentary) Lancet, vol. 362, October 18, 2003.
24. Henderson, S. T., "High carbohydrate diets and Alzheimer's disease. Med. Hypotheses 62: 689-700, 2004.
25. Rosedale, MD, Ron, "Insulin and Its Metabolic Effects," http://www.mercola.com/2001/jul/14/insulin2.htm" Accessed August 5, 2005.
26. Ho, et al., "Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease," The FASEB Journal express article 10.1096/fj.o3-0978fje. Epub March 19, 2004.
27. Pedersen and Flynn, "Insulin resistance contributes to aberrant stress responses in the Tg2576 mouse model of Alzheimer's disease," Neurobiology of Disease 17: 500-506, 2004.
28. http://www.dyets.com/110700.htm. Accessed August 5, 2005.
29. http://www.researchdiets.com/products/study/obesity.htm. Accessed August 5, 2005.
30. http://www.researchdiets.com/faq/faqs.htm#1. Accessed August 5, 2005.
31. Enig PhD, Mary, "Trans Fatty Acids Are Not Formed By Heating Vegetable Oils," WestonAPrice.org, http://www.westonaprice.org/knowyourfats/howtransform.html. Accessed August 5, 2005.
32. Enig PhD, Mary, Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils, and Cholesterol, Silver Spring: Bethseda Press, 2001, p. 43.