Oct
14
2017

A New Genetic Marker For Alzheimer’s

“A new genetic marker for Alzheimer’s”; so reported a study dated August 11, 2017. Most of all, they found that a genetic marker, TOMM40 was stronger than the established genetic marker APOE4. It seems like the older studies overlooked the importance of the new TOMM40 genetic marker. This new marker may have been present at the same time as APOE4.

Details of study regarding a new genetic marker for Alzheimer’s

The APOE4 is especially relevant for the formation of lipoproteins. APOE4 showed a strong association with the formation of amyloid plaque. This is located in the brain areas where Alzheimer’s disease developed. Therefore the thinking in the past was that APOE4 would be the culprit behind memory loss and Alzheimer’s disease. In contrast, the new study shows evidence that the TOMM40 genetic marker is the gene that actually orchestrates the development of Alzheimer’s disease. Thalida Em Arpawong is a postdoctoral fellow at the University of Southern California (USC) Dornsife College. She conducted research about the TOMM40 marker. Her supervisor was senior investigator Carol A. Prescott, who is a professor of psychology at the USC Dornsife College. She co-published the paper.

More info about the study involving a new genetic marker for Alzheimer’s

Professor Prescott used two verbal memory test results. They were the United States Health and Retirement Survey (HRS) and the English Longitudinal Study of Ageing (ELSA). In these tests immediate recall was compared to delayed recall 5 minutes later. Alzheimer’s patients have problems with short term memory recall.  In total the study examined 20,650 HRS participants and 11,391 ELSA participants. Their age was 50 years and above since this is the typical age for the onset of Alzheimer’s disease. Genetic data was part of the examination in 7,486 HRS participants and 6,898 ELSA participants. The scientists looked at 1.2 million genetic variations of the human genome to fit the memory loss. In conclusion, only one gene area, TOMM40 showed a strong association with decline in immediate and delayed memory recall.

Hence professor Carol A. Prescott summarized the findings: “The results from this study…raise the question of how many findings in other studies show an association with APOE4 that may in fact be due to TOMM40 or a combination of TOMM40 and APOE4.”

Possible future clues from a trial using TOMM40 marker

A review paper points out the start of a new trial, called TOMMOROW. The review paper points out that the location of APOE and TOMM40 are on chromosome 19 in very close proximity. Pioglitazone is a drug that controls diabetes. Patients tolerate it well. It is used in the TOMMORROW trial. As this review paper states the TOMM40 gene is responsible for the outer mitochondrion membrane. Consequently the paper states: the “outer mitochondrial membrane channel through which peptides and proteins travel into mitochondria to support mitochondrial function and biogenesis” is the key for understanding Alzheimer’s disease. Because pioglitazone is a drug that induces mitochondrial doubling the researchers hope that it will help Alzheimer’s patients.  It will probably be interesting to follow the phase 3 trial TOMMORROW, where research will observe the delay in onset of minimal cognitive impairment.

A New Genetic Marker For Alzheimer’s

A New Genetic Marker For Alzheimer’s

Conclusion

Research has found a new genetic marker for Alzheimer’s, TOMM40 that identifies a higher risk of getting Alzheimer’s disease. Its location is close to the marker APOE on chromosome 19. It appears that TOMM40 may be more reliable in identifying patients at risk for Alzheimer’s disease than the older APOE marker. As a result research has started a new phase 3 trial, called TOMMORROW. This will tell whether or not Pioglitazone, a diabetic drug maybe useful in delaying Alzheimer’s disease in high-risk patients.

ADDENDUM: This link shows that the TOMMORROW trial had to be shut down, because the drug Pioglitazone had no effect on slowing down the onset of Alzheimer’s disease.

Apr
15
2015

Avoid Brain Atrophy

When a 24-year old football player (Chris Borland) suddenly decides to quit his active sports career, because he wants to plan for a disability-free long life without brain atrophy, the world listens. Chris did his research about traumatic brain injuries, which can lead to degenerative brain disease or chronic traumatic encephalopathy (CTE). Trauma to the brain is just one cause of brain shrinkage (medically termed “brain atrophy”).

I like to take a broader overview of the topic of brain atrophy, which looks at all of the factors that can lead to brain shrinkage including physical injuries to the brain from blows to the head.

The vast majority of cases of brain shrinkage do not come from physical injuries, but rather from medical illnesses. Many of them including many sports injuries are preventable. This is the topic of my blog today.

Brain atrophy means a loss of brain cells, which causes a smaller brain. An MRI scan (around 800 to 1000$) will give information about the brain.The most sophisticated tool to depict the functioning of the brain may be the SPECT scan (ranging from 2000 to 2500$).

What causes brain atrophy?

It is important to realize that a multitude of different factors can cause the same end result – brain atrophy. All of these factors work together causing brain atrophy and the more factors are at play the worse the outcome. So, let’s review the various known causes of brain atrophy.

Diabetes

It has been known for a long time that diabetics can develop brain atrophy and dementia when their blood sugars are not well controlled. This leads to the formation of advanced glycation end-products (AGEs).

Insulin and IGF-1, a factor produced by the liver in response to human growth hormone have been found to counter the development of brain atrophy in diabetics.

The key in patients with diabetes is a close control of blood sugars, best measured as the hemoglobin A1C blood test. At the 22nd Annual World Congress on Anti-Aging Medicine In Las Vegas (Dec. 10-14, 2014) Dr. Theodore Piliszek stated that the new normal range for hemoglobin A1C is 3.8 to 4.9%, quite a bit lower than the normally recommended values. Accepting the old values that proclaim levels of 5.5. as normal automatically puts you in a higher risk of developing brain atrophy and dementia.

Cardiovascular disease

What is good for the heart is good for the brain. That is what Dr. Perlmutter stated in his book (Ref.1). But the reverse is also true: if your cardiovascular system is sick, your brain gets sick!

Here is a full-text article that describes how intimately connected heart function and brain function is.

Cardiovascular disease is a broad term and includes atrial fibrillation, blood clots in the coronary arteries or brain vessels (medically called “thrombotic events”), high and low blood pressure, heart failure, heart valve defects, low cardiac output, inflammation in the blood and a genetic marker, called Apo E, which is commonly associated with Alzheimer’s disease.

The end result of any of these conditions will cause brain atrophy. Once a problem is identified, it is important that the patient is seeing the appropriate specialist who will take care of the risk factor in order to prevent brain atrophy.

Vitamin B deficiency

Some people are born with a certain degree of a methylation defect, a deficiency of certain enzymes, which prevents methylation of brain hormones and other metabolic products. This can lead to depression, schizophrenia, memory loss and you guessed right: brain atrophy, which manifests itself as Alzheimer’s disease or dementia.

By using the proper nutrients with high enough supplements of vitamin B2, B6 and B12 this biochemical process can be restored and brain atrophy can be prevented. SAMe is also a useful supplement that supports methylation and a normal brain metabolism. Ref.2 explains methylation defects in more detail.

Obesity

The question is whether the “brain shrinks as the waist expands”. The answer is a clear “yes”. Researchers have found that the grey matter (with which we think) in the frontal lobes of the brain shrink in obese people of all ages. The researchers found further that the grey matter shrunk in the temporal and parietal parts of the brain of people in middle and old age.

The key here is to cut out refined carbs (sweetened sodas, pasta, bread, sugar in any form), as they are the ones that cause obesity. This occurs by the liver metabolizing sugar and turning it into fat that is stored. Just by cutting out sugar and starchy foods both my wife and I lost 50 pounds each in 2001. It can be done, but it takes a bit of will power.

The terminology may be confusing here: it is really sugar that causes brain atrophy via causing obesity and damage to the blood vessels.

Smoking and alcoholic beverages

Smoking leads to brain atrophy by damaging the blood vessels that are supposed to supply the brain with nutrients. If blood vessels close off or hardening of the arteries reduces the blood flow to the brain, brain cells die and brain atrophy develops.

Smoking also robs the body of vitamins, which slows down the brain cell function.

Alcohol is a nerve cell poison; it causes brain atrophy by directly damaging the brain cells (grey matter).

The results are memory loss, poor judgment, problems planning one’s future, loss of control with regard to emotions. This can lead to violent behavior and problems with regard to inter-personal relationships.

Genetic factors

ApoE4 gene variant, which causes inherited Alzheimer’s disease, causes a change of brain metabolism with deposits of a glue-like substance in the brain that damages nerve connections resulting in memory loss.

Researchers believe that ApoE4 is implicated in 20 to 25% of all Alzheimer’s cases.

Despite this apparent negative story, there is hope by radically changing one’s diet and taking supplements. Not every patient with one or two doses (alleles) of ApoE4 comes down with Alzheimer’s.

Avoid Brain Atrophy

Avoid Brain Atrophy

What can you do to prevent brain atrophy?

Supplements: Take regular B complex vitamins (particularly B2, B3, B6, folic acid, B12), vitamin E and C, carnosine, acetyl-L-carnitine, boron, ginger, coenzyme Q-10 (or CoQ-10), curcumin, vinpocetine, zinc, grape seed extract, blueberry extract, Ashwaganda, glyceryl-phosphoryl-choline, SAMe, huperzine A and DMAE. All of these have been found to support brain function and often restore memory function. Unfortunately regular anti-Alzheimer’s medications are not keeping their promise and on average just delay Alzheimer’s by 3 to 6 months. For details how these supplements work see this link.

Omega-3 fatty acids including DHA: These essential fatty acids from fish oil are very useful as they are anti-inflammatory and help support the normal brain metabolism, particularly DHA. In a Feb. 2015 US study from the Rhode Island Hospital 193 Alzheimer’s patients, 397 individuals with mild cognitive impairment and 229 normal individuals were followed for 5 years with MRI scans and cognitive tests every 6 months. 117 subjects were taking fish oil on a regular basis. The study showed a decline in gray matter in those who did not take fish oil and in carriers of the apolipoprotein E4 gene (a gene liked with Alzheimer’s disease). The gray matter on the MRI scans and brain function measure with cognitive function tests were much better preserved in those who took fish oil supplements.

Resveratrol: This powerful antioxidant is an anti-aging supplement. It is preventing heart disease, hardening of the arteries and helps preserve brain function by keeping the brain vessels from getting clogged up. DHA and omega-3-fatty acids are helping in that regard as well.

Eat nuts: Nuts are healthy (provided you are not allergic to them); but just because you are allergic to one kind does not mean you are allergic too all of them. Often a person allergic to hazelnuts will not be allergic to Macadamia nuts, cashew nuts or walnuts. Nuts contain a mixture of essential fatty acids, blood vessel friendly, saturated fatty acids and minerals that are all brain supportive.

Exercise regularly: Whoever moves and exercises keeps the heart healthy and whatever keeps the heart healthy keeps the brain healthy as stated before.

Stress management and sleep (avoid chronic overstimulation of your brain): In our hectic society everything has to be instant, the expectations of managers are high, the labor force is stressed. The fastest runner, the best player etc. is celebrated. The rest of us often feel like “underdogs”, if we allow this type of thinking to rule ourselves. Use yoga, self-hypnosis, meditation, religious mediation and prayer to counter some of the stress from everyday life. We need some stress to get us going, but we do not need “distress”. Dr. Hans Selye, the father of the general adaptation syndrome due to stress, gave a lecture about this topic in Hamilton, Ont. in 1977, which I attended. I vividly remember how he projected a picture of his skeleton showing bilateral hip replacements. He said that chronic stress could lead to arthritis. He had developed end stage arthritis in his hips and required total hip replacements on both sides. He wanted to illustrate that stress leads to physical consequences; it may be a heart attack in one person, a stroke in another, arthritis in a third. Constant overdrive has physical consequences.

Avoid sugar and starchy foods: I left this point as the last as it may be more difficult to understand. I started touching this topic under “obesity” above. An overload of refined carbs leads to an overstimulation of the pancreas pouring out insulin. Too much insulin (hyperinsulinemia) causes hormonal disbalance and leads to diabetes type 3, the more modern name for Alzheimer’s. All starch is broken down by amylase into sugar, so essentially you get a sugar rush from any starchy food as well. Too much sugar in the blood oxidizes LDL cholesterol, which leads to inflammation in the body. The consequence of this are the following conditions: hardening of the arteries, strokes, heart attacks, Alzheimer’s due to brain atrophy, arthritis, Parkinson’s disease and cancer. I have blogged about these topics in many separate blogs.

Conclusion

In this blog I have reviewed how brain atrophy develops. There are a multitude of factors that over a lifetime can lead to brain atrophy. Repetitive head trauma from contact sports is only one reason; poor nutrition with too much sugar and starch and missing essential fatty acids (omega-3/DHA) is another potential cause. Add to this a lack of exercise, too much stress, alcohol and smoking and you covered most of the causes. Studies have shown that even when you carry the ApoE4 gene trait, only 30% will express it as supplements can suppress the expression of it. The key is prevention. Preserve your brain cells, prevent brain atrophy!

References:

Ref. 1: David Perlmutter, MD: “Grain Brain. The Surprising Truth About Wheat, Carbs, And Sugar-Your Brain’s Silent Killers.” Little, Brown and Company, New York, 2013.

Ref.2: William J. Walsh, PhD: “Nutrient Power. Heal your biochemistry and heal your brain”. Skyhorse Publishing, 2014.

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