Rodents acquired Alzheimer's-like brain abnormalities on diets designed to mimic typical fast foods 12/02/2008
An estimated 5.2 million Americans suffer from Alzheimer's disease, and the toll it takes on their families may well exceed the patients' own suffering.
The results of a study from Sweden heighten suspicions that diets dominated by junky fast food meals damage brains in addition to harming heart and overall health.
By “fast food meals” we mean ones that share two characteristics:
- High in sugars, refined flours and starches, saturated and omega-6 fats (from animal fat and vegetable oils), and cholesterol.
- Low in (mostly colorful) plant foods rich in fiber and antioxidant, anti-inflammatory factors.
Sugary, starchy foods tend to promote generation of pro-oxidant, pro-inflammatory free radicals, as do omega-6 fats and fried or browned foods.
The damage done to brain (and other) cells by free radicals and the inflammation they induce raise the risk of Alzheimer's.
Population studies link diets rich in antioxidants (and omega-3s) to reduced rates of Alzheimer's, and studies in dogs with Alzheimer's-like disease show clear improvements after increasing their intake of dietary antioxidants.
However, it remains unclear whether antioxidant supplements work as well for humans as for canines, and which ones are most effective (Akterin S et al. 2006; Praticò D 2008; Head E 2008).
Research in recent years also shows that, in genetically susceptible animals and people, diets high in cholesterol can produce the brain tissue changes that precede Alzheimer's disease and grow over time.
Of course, many fast-food meals contain clear excesses of the risk factor foods: omega-6 fat, cholesterol, sugar, and refined starches.
All of these factors appear to raise risk of Alzheimer's disease, but cholesterol appears risky only for people who carry a certain gene variant called APOE4.
We'll explain this major, gene-driven risk factor, and then summarize the new mouse study.
That new mouse study affirms the apparent dangers of fast food diets to mice bred to bear the inefficient APOE4 cholesterol-transport gene (or to lack any APOE gene at all)... and to the one in five Americans who share the APOE4 gene.
Having the APOE4 gene raises a bearer's risk of developing Alzheimer's disease—by far the most common form of dementia—from a substantial to a drastic degree, depending on how many copies of the gene he or she possesses.
How cholesterol can combine with a common gene variant to raise Alzheimer's risk
The risk-raising APOE4 gene is a variant of the gene that governs the production of a cholesterol- and fat-transport protein called apolipoprotein E.
People who carry the APOE4 gene are much more likely to develop the brain abnormalities characteristic of Alzheimer's disease, and to later show symptoms of Alzheimer's.
The APOE gene produces a protein that sits on the surface of lipoproteins that carry fats and cholesterol in the blood, helping direct triglyceride-type fats to cells that need them and, once delivery is complete, helping the liver remove cholesterol-laden lipoproteins from your blood.
APOE comes in three versions, E2, E3 and E4. E3 is the “normal” version that most people have. The less common E2 version is unusually efficient, and people with E2 tend to have low cholesterol levels.
APOE4 is the slacker in the crowd—the guide-protein it produces doesn't work very well, so more cholesterol gets left behind in the bloodstream.
While high cholesterol levels do not cause atherosclerosis—the buildup of fatty plaque in the coronary arteries that often leads to heart attacks and strokes—they do increase the risk of atherosclerosis.
This is especially true when diets are high in pro-inflammatory foods such as sugars, refined flours and starches, and omega-6 fats (from vegetable oil), but low in colorful, fiber- and antioxidant-rich plant foods: a description that fits typical fast food meals to a "T".
The APOE version that people have accounts for about 10 to 20 percent of their cholesterol levels, regardless of diet or exercise. And having APOE4 increases a person's risk of cardiovascular disease by 50 percent.
But it may play an even more significant role in the risk for late-onset Alzheimer's disease, the most common form, which strikes people over 65.
In fact, APOE4 raises Alzheimer's risk much more than the risk of heart disease. However, its means of promoting Alzheimer's are comparatively unclear.
One hypothesis involves the formation of one of the hallmarks of Alzheimer's: plaques made of an altered brain protein.
These plaques consist largely of a protein called beta amyloid peptide. The APOE4 gene binds readily to beta amyloid peptide, converting it from a soluble to an insoluble, harmful form.
As with any other gene, all people have two copies of the E2, E3 or E4 versions of APOE, in any and all combinations.
Having one copy of the E4 version triples the normal risk for late-onset Alzheimer's, while having two copies raises the risk 20-fold.
But in this case, genes are not destiny. You can acquire Alzheimer's without having the APOE4 gene, and having the gene does not make Alzheimer's inevitable.
New animal evidence from Sweden indicates that people with the APOE4 gene who eat a fast food, high-cholesterol diet may raise their Alzheimer's risk even higher.
These striking research results suggest that routine consumption of such fast-food meals can raise the risk of Alzheimer's… at least in mice made bred to carry the the APOE4 gene.
Mice fed fast-food fare suffer brain damage
A doctoral student at Stockholm's famed Karolinska Institute tested the effects of fast-food-like diets in mice bred to carry the risky APOE4 variant of the apolipoprotein E gene.
|Susanne Akertin of the Karolinska Institute|
The mice developed brain abnormalities like those seen in Alzheimer's patients.
Three years ago, her team published a study on mice bred to lack the apolipoprotein E gene entirely. Like people or mice with the APOE4 variant of the gene, such mice build up cholesterol in the blood.
The results showed that in mice that lacked the apolipoprotein E gene, high-cholesterol diets promote “over-phosphorylation” of a normal mouse and human brain protein called tau.
Over-phosphorylation of tau causes this otherwise normal brain protein to form the neurofibrillary “tangles” seen in Alzheimer's disease, which damage brain cells and eventually kill them (Rahman A et al. 2005).
After the current study, Ms. Akterin's team discovered increased over-phosphorylation of tau proteins in the mice they fed fast-food-like diets.
And in a study published earlier this year, they found that animals on high-fat/cholesterol diets suffered lowered levels of a brain compound called Arc (activity-regulated cytoskeleton-associated protein), which is needed for memory (Mateos L et al. 2008).
As Ms. Akterin said in a press release, “We now suspect that a high intake of fat and cholesterol in combination with genetic factors, such as APOE4, can adversely affect several brain substances, which can be a contributory factor in the development of Alzheimer's.”
For now, people with the APOE4 gene should watch their cholesterol intake.
But it's premature to conclude that people without the risky APOE4 gene need to cut back on dietary cholesterol.
Instead, the results of animal studies simply affirm that junky fast-food diets are generally unhealthful because they lack whole plant foods and are loaded with nutritionally “empty” calories from pro-inflammatory sugars, starches, and omega-6 fats.
Be wary of what you eat... long-term habits can change your brain for good or ill.
- Akterin S, Cowburn RF, Miranda-Vizuete A, Jimenez A, Bogdanovic N, Winblad B, Cedazo-Minguez A. Involvement of glutaredoxin-1 and thioredoxin-1 in beta-amyloid toxicity and Alzheimers disease. Cell Death Differ, 2006; 13(9): 1454-65. Epub 2005 Nov 25
- Akterin S. Thesis: From cholesterol to oxidative stress in Alzheimer's disease: A wide perspective on a multifactorial disease. Department of Neurobiology, Care Sciences and Society, KI Alzheimer's Disease Research Center, Karolinska Institutet, Stockholm, Sweden. ISBN: 978-91-7409-172-4 / Diss: 08:312. Accessed online November 30, 2008 at http://diss.kib.ki.se/2008/978-91-7409-172-4/
- Head E. Oxidative Damage and Cognitive Dysfunction: Antioxidant Treatments to Promote Healthy Brain Aging. Neurochem Res. 2008 Aug 6. [Epub ahead of print]
- Mateos L, Akterin S, Gil-Bea FJ, Spulber S, Rahman A, Björkhem I, Schultzberg M, Flores-Morales A, Cedazo-Minguez A. Activity-Regulated Cytoskeleton-Associated Protein in Rodent Brain is Down-Regulated by High Fat Diet in vivo and by 27-Hydroxycholesterol in vitro. Brain Pathol, 2008; May 23: Epub ahead of print
- Praticò D. Oxidative stress hypothesis in Alzheimer's disease: a reappraisal. Trends Pharmacol Sci. 2008 Dec;29(12):609-15. Epub 2008 Oct 4.
- Rahman A, Akterin S, Flores-Morales A, Crisby M, Kivipelto M, Schultzberg M, Cedazo-Minguez A. High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice. FEBS Lett, 2005; 579(28): 6411-6. Epub 2005 Nov 2