Tau vs. Amyloid - An Alzheimer's Dilemma

For starters, this post is not about a sporting event, even though the title might lead one to think otherwise. The fact is there have been different approaches regarding research of the basic cause of Alzheimer's (AD), and hopefully, an eventual treatment and cure. The focus has been on protein changes in the brain.

The majority of the Alzheimer's research field has mainly focused on the protein ß-amyloid over the last 25 years. Brain scans performed over the last decade revealed that amyloid accumulated as AD progressed, so most Alzheimer's models are based on amyloid toxicity. (It has been found that amyloid can start accumulating in the brain by age 20).

The evidence however, left something to be desired. Even though studies have demonstrated that as a general rule, people with AD have far more ß-amyloid plaques in their brains than non AD people,  studies have also revealed a puzzle: roughly 30% of people without any signs of dementia have brains “chock-full” of ß-amyloid at autopsy, said neurologist Beau Ances at Washington University in St. Louis in Missouri. This finding has been well known for many years.

Could something else be the real cause of AD? Something like tau, which is a protein found in neurons (nerve cells)?

In an article published in Brain in 2015 researchers at the Mayo Clinics in Florida and Minnesota
concluded that tau is the culprit. The researchers were able to simultaneously look at the evolution of amyloid and tau using neuropathologic measures (over 3500 brain autopsies and scans).

The lead author, Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic stated: "Imagine looking at the rings of a tree—you can identify patterns, like the changing seasons and the aging of the tree, when viewing the tree's cross-section...Studying brains at different stages of Alzheimer's gives us a perspective of the cognitive impact of a wide range of both amyloid and tau severity. Tau can be compared to railroad ties that stabilize a train track that brain cells use to transport food, messages and other vital cargo throughout neurons. In Alzheimer's, changes in the tau protein cause the tracks to become unstable in neurons of the hippocampus, the center of memory. The abnormal tau builds up in neurons, which eventually leads to the death of these neurons. Evidence suggests that abnormal tau then spreads from cell to cell, disseminating pathological tau in the brain's cortex. The cortex is the outer part of the brain that is involved in higher levels of thinking, planning, behavior and attention mirroring later behavioral changes in Alzheimer's patients"

She continued: "Our study shows that the accumulation of amyloid has a strong relationship with a decline in cognition. When you account for the severity of tau pathology, however, the relationship between amyloid and cognition disappears—which indicates tau is the driver of Alzheimer's."

Furthermore, Dr. Murray noted, "Our findings highlight the need to focus on tau for therapeutics, but it also still indicates that the current method of amyloid brain scanning offers valid insights into tracking Alzheimer's."

At the current time, there is not an accurate way to measure tau. Of particular interest is that large pharmaceutical firms, trying to find a treatment for AD, are spending hundreds of millions of dollars to develop drugs that try to stop or slow down amyloid deposits.

America....world...stay tuned.

Brain scans performed over the last decade revealed that amyloid accumulated as people progressed, so most Alzheimer's models were based on amyloid toxicity

Read more at: https://medicalxpress.com/news/2015-03-thousands-brains-reveals-tau-driver.html#jCp

Brain scans performed over the last decade revealed that amyloid accumulated as people progressed, so most Alzheimer's models were based on amyloid toxicity

Read more at: https://medicalxpress.com/news/2015-03-thousands-brains-reveals-tau-driver.html#jCp

Brain scans performed over the last decade revealed that amyloid accumulated as people progressed, so most Alzheimer's models were based on amyloid toxicity

Read more at: https://medicalxpress.com/news/2015-03-thousands-brains-reveals-tau-driver.html#jCp

Memory as a Predictor

We are all aware that memory disturbances are a prominent feature of dementia, 75% of which is classified as Alzheimer's. As studies continue to try to shed some light on this dreaded condition, we are slowly dissecting some pre-Alzheimer's conditions that might shed light on what to expect in terms of our own future vulnerabilities. In fact, 90% of what we know about Alzheimer’s has been discovered in the last 15 years. What to expect includes invasive and non-invasive testing.

MCI, or Mild Cognitive Impairment, is a condition where cognitive changes are serious enough to be noticed by the individuals experiencing them or to other people but are not severe enough to interfere with daily life or independent functions.  Currently there are 2 recognized types of MCI.

MCI that primarily affects memory is known as "amnestic MCI." With aMCI, a person loses episodic memory and may start to forget valuable information that he or she would previously have recalled easily, such as appointments, conversations or recent events.  People with aMCI are more likely to develop Alzheimer's.

MCI that affects thinking skills other than memory is known as "non-amnestic MCI." Thinking skills that may be affected by non-amnestic MCI include the ability to make sound decisions, judge the time or judge a sequence of steps needed to complete a complex task.

Some MCI cases stay the same; some can revert to normal. Why this is we do not yet know. The chance of progressing to Alzheimer's from any MCI are dependent on multiple factors, so there is no clear number percentage of what to expect in any given individual. In general, it has been reported that there is around a 50% chance of developing Alzheimer's within 5 years.

One predictive test uses electroencephalogram (EEG) technology, a more affordable and non-invasive alternative compared to other methods (such as PET scans) to measure neural responses. In a study published in the Journal of Alzheimer's Disease, scientists found that individuals with amnestic mild cognitive impairment (aMCI) have twice the risk of others in their age group of progressing to Alzheimer's after identifying a specific variation in their brain waves.  These EEG findings reveal a  pattern of delayed neural activity that is directly related to the severity of cognitive impairment during a word task and may indicate an early progression to Alzheimer's.

After more vetting, the prospective EEG diagnostic tool could potentially provide complementary information for diagnosis of pre-dementia stages, including MCI, and possibly identify neural changes that precede cases of Alzheimer's disease.

In a study published in the Journal of Alzheimer's Disease, scientists found that individuals with amnestic mild cognitive impairment (aMCI) have twice the risk of others in their age group of progressing to Alzheimer's after identifying a specific variation in their brain waves.

Read more at: https://medicalxpress.com/news/2015-09-alzheimer.html#jCp

In a study published in the Journal of Alzheimer's Disease, scientists found that individuals with amnestic mild cognitive impairment (aMCI) have twice the risk of others in their age group of progressing to Alzheimer's after identifying a specific variation in their brain waves.

Read more at: https://medicalxpress.com/news/2015-09-alzheimer.html#jCp

In a study published in the Journal of Alzheimer's Disease, scientists found that individuals with amnestic mild cognitive impairment (aMCI) have twice the risk of others in their age group of progressing to Alzheimer's after identifying a specific variation in their brain waves.

Read more at: https://medicalxpress.com/news/2015-09-alzheimer.html#jCp

In a study published in the Journal of Alzheimer's Disease, scientists found that individuals with amnestic mild cognitive impairment (aMCI) have twice the risk of others in their age group of progressing to Alzheimer's after identifying a specific variation in their brain waves.

Read more at: https://medicalxpress.com/news/2015-09-alzheimer.html#jCp

In a study published in the Journal of Alzheimer's Disease, scientists found that individuals with amnestic mild cognitive impairment (aMCI) have twice the risk of others in their age group of progressing to Alzheimer's after identifying a specific variation in their brain waves.

Read more at: https://medicalxpress.com/news/2015-09-alzheimer.html#jCp

Diet and Alzheimer's

Much has been published about the interrelationship between diet, lifestyle and AD. The following advice was posted by Dr Stephen Sinatra, a prominent and respected cardiologist who brought attention to the world of taking CoQ 10. He is the medical director of the HeartMD Institute
It should be noted that it's always best to try to eat organic foods.

1. The healthiest diets on the planet, associated with the lowest incidence of chronic illnesses, are the traditional Mediterranean and Asian diets.

2. Research says unequivocally that the more vegetables you eat, the less susceptible you will be to age related memory problems. The types of vegetables that offer the most protection are leafy greens like spinach, and the cruciferous varieties such as broccoli, cauliflower, and kale.

3. Avoid or significantly reduce sugar and refined carbohydrates. We over consume these problematic foods. They increase blood sugar and insulin levels, triggering inflammation and eventually diabetes, and are linked to Alzheimer’s and other forms of dementia.

4. Be sure to include a variety of fresh fruit in your diet, especially antioxidant rich berries. 
 Blueberries, in particular, are high in specific antioxidants called anthocyanins that can actually enhance your brain cells’ ability to communicate with each other.

5. Recent research suggests that heart healthy HDL cholesterol not only protects against heart disease and stroke but can provide protection against dementia as well. The best way to raise your HDL level is to make vegetables and fruits the largest part of your diet.

6. Make sure you get enough B vitamins in your diet, especially folate (folic acid). Inadequate folate can triple your risk of dementia later in life. Foods rich in folate include leafy green vegetables such as turnip greens and spinach, and legumes like chickpeas and kidney beans.

7. The combination of antioxidant-rich spinach and free-range, organic eggs packs quite a memory-boosting punch. The healthy fat in egg yolk allows beneficial nutrients in the spinach to be fully absorbed by the body.

8. Go for garlic. In addition to its pungent aroma, garlic packs antioxidants with the power to reduce inflammation involved in cognitive issues.

9. Eat healthy, anti-inflammatory fats by consuming plenty of nuts, fish such as wild-caught salmon and sardines, and avocados on a daily basis. They protect and fortify brain function. And don’t forget the extra virgin olive oil! (Blog editor's note - it has been reported that wild caught salmon from the Pacific Northwest may be contaminated with parasites)

10. A glass of red wine up to six times a week has been found to benefit brain function. It slows down mental decline, according to research. Drinking more does not help.

11. The curry spice turmeric and its pigment extract curcumin rank among the most potent food- derived anti-inflammatory agents. In a study, curcumin appeared to have a destructive effect on plaque in the memory circuits of the brains of Alzheimer’s patients.

12. Introduce flavorful cinnamon into your diet by sprinkling onto smoothies, whole grain cereal, and fruit. Cinnamon provides a strong antioxidant effect and helps stabilize blood sugar.

For additional information, click on this line Dementia Diet

Will I Inherit Alzheimer's Disease? The Interaction of the Environment and Genetics

There is a wealth of new research for Alzheimer's disease that seems very promising for the future.

So where does one begin? In this post I am going to review our current understanding of the role of genetics and epigenetics (environmental factors) in developing Alzheimer's disease (AD). Many people are wondering whether they will inherit AD if someone in the family has been afflicted. The answer is clearly not necessarily, as explained below.

Much of the following information is culled from the National Institute of Aging and Medscape

There are two types of Alzheimer's disease - Early-onset and Late-onset (LOAD

Early-onset familial Alzheimer's disease

Early-onset Alzheimer's disease occurs in people age 30 to 60. It is rare, representing less than 5 percent of all people who have Alzheimer's. Some cases of early-onset Alzheimer's have no known cause, but most cases are inherited, a type known as familial Alzheimer's disease (FAD).

Familial Alzheimer's disease is caused by any one of a number of different single-gene mutations on chromosomes 21, 14, and 1. Each of these mutations causes abnormal proteins to be formed.

The single-gene mutations directly responsible for early-onset Alzheimer's disease do not seem to be involved in late-onset Alzheimer's.


LOAD - Late-Onset Alzheimer's Disease

Genetic change can cause a disease directly, but more often acts to increase or decrease a person's risk of developing a disease. This it is called a genetic risk factor. We are now learning that genes can be changed by our environment.

Most cases of Alzheimer disease are the late-onset form, which develops after 60 years of age. The causes of late-onset Alzheimer disease include a combination of genetic, environmental, and lifestyle factors that influence a person's risk for developing Alzheimer disease. The inheritable risk in LOAD is 60-80%, but genetics and environmental factors equally contribute to the onset, progression, and severity of disease.

Researchers have not found a specific gene that causes the late-onset form of the disease. However, one genetic risk factor does appear to increase a person's risk of developing the disease. This increased risk is related to the apolipoprotein E (APOE) gene found on chromosome 19.  APOE comes in several different forms.

• APOE ε2 gene is relatively rare and may provide some protection against the disease. If Alzheimer's disease occurs in a person with this gene, it develops later in life than it would in someone with the APOE ε4 gene

• APOE ε3, the most common gene, is believed to play a neutral role in the disease—neither decreasing or increasing risk.

• APOE ε4 gene is present in about 10 to 15 percent of the population and in about 40 percent of all people with late-onset Alzheimer's. People who develop AD are more likely to have the APOE ε4 gene and tend to develop the disease at an earlier age than those who do not have any APOE ε4 genes.

Although a blood test can identify which APOE genes a person has, it cannot predict who will or will not develop Alzheimer's disease. It is unlikely that genetic testing will ever be able to predict the disease with 100 percent accuracy because too many other factors may influence its development and progression.

One of the biggest limitations of genetic testing is the psychological impact that positive results can have on patients who might have the disease in the future. Surprisingly, the impact of delivering a positive result was studied by the REVEAL trial, which didn’t show any significant long-term psychological impact, depression, or anxiety in patients testing positive for the APOE ε4 gene

The Good News

Epigenetics - The Interaction of Environment and Genetics

Scientists have long thought that genetic and environmental factors interact to influence a person's biological makeup, including the predisposition to different diseases. More recently, they have discovered the biological mechanisms for those interactions. The expression of genes (when particular genes are “switched” on or off) can be affected - positively or negatively - by environmental factors such as stress, exercise, diet, chemicals, or smoking.

Epigenetics is an emerging frontier of science focused on how, and when, particular genes are expressed. Diet and exposure to chemicals in the environment, among other factors throughout all stages of life, can alter a cell's DNA in ways that affect the activity of genes that can make people more or less susceptible to developing a disease later in life. There is emerging evidence that epigenetic mechanisms contribute to Alzheimer's disease. Epigenetic changes, whether protective, benign, or harmful, may help explain why one family member develops the disease and another does not.

Thus it is clear that development of late acting Alzheimer's disease is not written in stone, even with the presence of the APOE ε4 gene. Lifestyle choices can indeed mediate its outcome.

May 6, 2015

Welcome to the Alzheimer's Updates Digest blog.

As we are all aware, Alzheimer's disease has been in the media spotlight recently due to its increasing frequency in the population and its devastating effects on the patient and the circle of family, friends and caregivers. Most distressing is the almost total lack of effective treatment.

Alzheimer's disease has been called The Long Goodbye. Its insidious course leaves behind emotional outrage, exhaustion and frustration. It spares no social, educational or achievement level.

How exasperating it is to witness a person’s entire life wither away and go to some dark place that will never see light again.

How exasperating it is to witness a person’s essential being disappear into a void without rhyme or reason.

Yet there is hope. There MUST BE HOPE that one day, with concerted effort and perhaps sooner than anticipated, this dreadful malady will be cured, arrested or prevented. There is no doubt that the human ingenuity that took us to the moon, that created smart phones and solar energy, that changed the genotype will indeed conquer Alzheimer's.

The purpose of this blog is to periodically summarize the various studies and insights that have or are now contributing to the goal of eliminating this disastrous disease

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