Dietary Choline

Biodesign researchers at the Arizona State University - Banner Neurodegenerative Disease Research Center (NDRC) looked into whether the nutrient choline could alleviate the effects of Alzheimer's by studying AD mice.

 

All plant and animal cells require choline to maintain their structural integrity. It has long been recognized that choline is particularly important for brain function.

 

Studies in the AD mice found that choline acts to protect the brain from Alzheimer's disease in at least two ways. First, choline blocks the production of amyloid-beta plaques. Second, choline supplementation reduces the activation of microglia, which when overactive can cause death of brain cells.

From a human perspective, the authors noted that while no one factor determines the cause or clinical course of Alzheimer's, a recent report found that the increase in cases of dementia in the United Kingdom may be associated with a lack of choline in the diet throughout life. Another report suggested that plant-based diets may be detrimental due to the lack of important nutrients, including choline.

 

The current established adequate intake level of choline for adult women is 425mg/day, and 550mg/day for adult men. This recommended daily intake (RDI) may not be optimal, especially in women, given the higher incidence of AD seen in women. This suggests that additional choline in diet may be beneficial in preventing harmful changes associated with the aging brain.

 

According to the United States Department of Agriculture (USDA), high levels of choline are found in chicken liver (3oz; 247mg), eggs (1 large egg with yolk; 147mg), beef grass-fed steak (3oz; 55mg), wheat germ (1oz toast; 51mg), milk (8oz; 38mg), and Brussels sprouts (1/2 cup; 32mg).

 

The authors further noted that choline is an attractive candidate for prevention of AD, as it is considered a very safe alternative compared with many pharmaceuticals. "At 4.5 X the RDI, we are well under the tolerable upper limit, making this a safe preventive therapeutic strategy."

 

Arizona State University. "Common nutrient supplementation may hold the answers to combating Alzheimer's disease." ScienceDaily. www.sciencedaily.com/releases/2019/09/190927122526.htm (accessed November 27, 2019).

Could it be the Micobiome?

More and more evidence is piling in about the effect of the microbiome on our health, and in this entry, on brain disorders. It should be noted that while the microbiome is often referred to as in the gut, it exists in many other body parts, an example being our skin.

IBS

An article published in the US version of the Guardian asked if the microbiome is the key to health and happiness. it was reported that "The gut microbiome is a vast ecosystem of organisms such as bacteria, yeasts, fungi, viruses and protozoans that live in our digestive pipes, which collectively weigh up to 4.4 lbs. (heavier than the average brain). It is increasingly treated by scientists as an organ in its own right. Each gut contains about 100 trillion bacteria, many of which are vital, breaking down food and toxins, making vitamins and training our immune systems".The article also noted that "eight years ago, an investigation into irritable bowel syndrome drew (his)  gaze towards the gut. Like people with depression, those with IBS often report having experienced early-life trauma, so in 2009, John Cryan and his colleagues set about traumatising rat pups by separating them from their mothers. They found that the microbiome of these animals in adulthood had decreased diversity".

Depression

In work done at the Children's Hospital of Phildelphia it was recently reported that microbiome transplants affected depression in rats (one has to kind of wonder how we really know rats are depressed). "In rats that show depressive-type behavior in a laboratory test, we found that stress changes their gut microbiome -- the population of bacteria in the gut," said study leader Seema Bhatnagar, PhD, a neuroscientist in Department of Anesthesiology and Critical Care at Children's Hospital of Philadelphia (CHOP). "Moreover, when we transplanted bacteria from those stress-vulnerable rats into rats that had not been stressed, the recipient animals showed similar behavior."

Alzheimer's

Of course it was inevitable that the linking of Alzheimer's to the microbiome would need to be studied. Sure enough, this December past, the University of Chicago announced that Sangram Sisodia, Ph.D. will be doing  a research study that "will investigate the roles of the gut and brain microbiome on Alzheimer's disease and its related symptoms in humans and mice, particularly their interactions with immune cells and genes, and influence of the blood-brain barrier on these processes"

There will undoubtedly be many more studies to come on how the microbiome affects all aspects of our lives. There will be many surprising and mind shattering results that will change the way we understand disease and advance medical diagnosis and treatment. This is just the tip of the iceberg. And yes, it may very well be the key to our health and happiness (and unfortunately to disease and sadness).

"Is your gut microbiome the key to health and happiness?"Amy Fleming. The Guardian. Nov 6, 2017. https://www.theguardian.com/lifeandstyle/2017/nov/06/microbiome-gut-health-digestive-system-genes-happiness

Children's Hospital of Philadelphia. "Transplanting gut bacteria alters depression-related behavior, brain inflammation in animals: Knowledge of stress biology may eventually yield bacterial treatments for psychiatric disorders." ScienceDaily. www.sciencedaily.com/releases/2019/05/190506163642.htm (accessed May 7, 2019).

 https://www.uchicagomedicine.org/forefront/microbiome-articles/2018/december/neuroscientist-receives-grant-to-study-microbiome-and-alzheimers

Alzheimer's Research Caveats

Alzheimer's research is in the news more than ever as cultural and political factors enter the discussion. AD is such a terrible, incurable process, and affects so many families, that it is not surprising that the goal to find a cure is accelerating at a rapid pace.

One great example is in 2018 Bill Gates announced that a coalition of philanthropists have committed  $30 million for research on promising and innovative ideas to diagnose the early onset of AD before symptoms occur. The designation is the Diagnostics Accelerator fund. This approach is probably the most promising, as it known that whatever causes the onset of AD seems to occur 10-20 years prior to symptoms.

The other approach of research is the development of drugs and associated clinical trials that attempt to arrest, cure (or prevent)  AD. Over the years this has been largely ineffective. One emerging consensus is that once changes take place in the brain they are irreversible, so drugs won't work. Another is that treatments are begun too late in the course of the disease i.e- symptoms have already developed. Both are probably correct.

Yet research continues, mostly centered around amyloid, which is often associated with AD. Some new research is about tau. No meaningful positive results have occurred even as billions of dollars are spent on AD research. This blog has attempted to highlight some of these issues in previous posts.

One problem plaguing all medical research, including AD, is the not usually talked about conflicts of interest. Too often articles are published, even in prestigious medical journals, touting the latest and greatest drug, only to be proven inadequate upon further and/or independent testing. Many published researchers are paid by the pharmaceutical industry to study drugs in development. Unfortunately, some researchers are dependent on the largess of drugs firms for future funding and may not be as objective as one might  expect. The worst thing is that many times the conflict is not revealed by the researchers, so the public has no way of knowing.  Conflicting results from different researchers can be confusing,

Now the latest theories about cause and effect involve infectious diseases. More will come about this in future blogs. So, at this stage, we still seem to be floundering. Lots of thoughts, lot of money, lots of frustration. Where will it lead? AD is indeed very complicated.



https://www.medscape.com/viewarticle/899446

Gum Disease - the Root Cause of AD?

We are in EXCITING times.

• It is quite possible that we may now know a cause of AD.
• It is quite possible that we may have finally found an effective treatment.

A research paper* published just a few days ago reveals the bacteria, P. gingivali, which causes gingivitis of the gums, may be a cause of AD. Furthermore, it suggests that treating and/or preventing P. gingivali infections may very well reverse or prevent AD.

The findings include that P. gingivali is found in the associated parts of the brain of people who have AD. A toxin secreted by the bacteria (gingipain) is present in the amyloid and tau plaques associated with AD. This toxin destroys neurons (nerve cells) and causes protein damage. It is proposed that chronic, low-level inflammation of the brain caused by P. gingivali can lead to brain changes that cause AD. 

The article points out that "P. gingivalis is mainly found during gingival and periodontal infections; however, it can also be found at low levels in 25% of healthy individuals with no oral disease. Transient bacteremia of P. gingivalis can occur during common activities such as brushing, flossing, and chewing, as well as during dental procedures". Bacteremia is when bacteria get in the bloodstream, which explains how it can settle in brains. The bacteria has also been found in the spinal fluid of AD patients.

Antibiotics were used to control P. gingivali but were not as effective as a new drug that blocks the effects of the gingipain toxin. While much of the research was done on mice, the new drug is now being given to humans in a limited, controlled study. Preliminary results show the drug is safe and is already starting to improve AD. If all goes well a vaccine may eventually become available.

A key finding was that the presence of P. gingivali was not the result of AD, but rather could be the cause.

*Porphyromonas gingivalis in Alzheimer’s disease brains: Evidencefor disease causation and treatment with small molecule inhibitors. Stephen S.Dominy et. al. Science Advances 23 Jan 2019: Vol. 5, no. 1, eaau3333 DOI:10.1126/sciadv.aau3333

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Zombies of Alzheimer's Disease (AD)

In a previous blog post Tau vs. Amyloid - An Alzheimer's Dilemma
I wrote about Tau as a mitigating factor in AD. Lately there is more and more attention being paid about Tau.

In a recent published report* Tau has been referenced in a creative interpretation of zombie like cells, more scientifically referred to as senescent cells. In the life cycle of a cell there is a senescence period when the cell becomes stressed and has ceased it's normal function. At this stage it can actually cause more harm than good.

According to senior author Miranda E. Orr, Ph.D., VA research health scientist at the South Texas Veterans Health Care System, "When cells enter this stage, they change their genetic programming and become pro-inflammatory and toxic"  These cells then secrete a substance that kills adjacent healthy cells.

Although the study was done in mice, it was found that tau proteins surrounding cells caused cell senescence. Furthermore, senescence was not found with amyloid.  In other studies to confirm this, reducing tau genetically also reduced senescence. The reverse also held true. Increasing tau genetically increased senescence.

When the researchers used a combination of the drugs dasatinib and quercetin cellular senescence decreased and brain structure and function improved. In fact the drugs were able to clear the tau pathology and stop, or even reverse, the progression of AD.

While much work has to be done, the authors believe that the effects of the drug combination may work in human being to reduce senescence. More clinical studies are necessary.


*University of Texas Health Science Center at San Antonio. (2018, August 22). Stressed, toxic, zombie cells seen for 1st time in Alzheimer's: Finding may apply to 20 brain diseases; drug tandem stops decline in old mice. ScienceDaily. Retrieved November 20, 2018 from www.sciencedaily.com/releases/2018/08/180822092706.htm

Can the Eyes Have It? Can Eye Scans Predict Alzheimer's?

Here is some news hot off the press! This news was just released a few days ago.

Being a retired ophthalmologist, I find these findings are unusually interesting and dear to my heart. More importantly, they are phenomenally earth shattering if the results are independently confirmed in the future.

Two papers were presented at the 2018 meeting of the American Academy of Ophthalmology that may make the prediction of future Alzheimer's (AD) onset and progression earlier and less costly with relatively non-invasive eye tests.

1 - Retinal Thickness Study

The first study, as reported by Ygal Rotenstreich, MD, e.t al. of the Goldschleger Eye Institute at Sheba Medical Center, Tel Aviv, Israel. involved measuring the thickness of the retina (inner lining of the eye).

The study showed that people with a family history of Alzheimer's had thinner inner layers of their retinas and corresponding thinning of the hippocampus, which was separately measured by a brain scan. Of particular note is that none of the patients studied had any symptoms of AD or MCI.

The hippocampus is the part of the brain greatly responsible for memory and is invariably thinned as AD progresses.

Rotenstreich stated that “Inner retinal layer thickness is associated with cognitive function and hippocampal volume and may present a novel bio-marker for very early detection of Alzheimer's  disease.”

The implication of this study means that AD can possibly be diagnosed much earlier than any study currently available.


2 - Retinal Blood Vessels Study 

This study, led by Sharon Fekrat, MD, and Dilraj Singh Grewal, MD, both of Duke University in Durham, NC, consisted of multiple eye studies of patients over 50 years old from the Duke Memory Disorders Clinic with AD or MCI as well as community-based healthy volunteers without known memory problems. In short, it was found that blood vessels in the eye may be a predictor of the progression of AD.

Findings concluded that patients with AD had significantly reduced retinal small vessel density and perfusion density (flow characteristics) compared to patients with mild cognitive impairment (MCI) and the normal volunteers. Perfusion density was also lower in MCI patients compared to the normals.

The retinal microvasculature (very small blood vessels) was measured by optical coherence tomography angiography, which is a relatively non-invasive procedure compared to current diagnostic tools such as spinal taps or not readily available and expensive PET scans.

It was concluded that changes in the retinal micro-vasculature may mirror small-vessel cerebrovascular (brain) changes in Alzheimer disease. The findings suggest a continuum of decreasing retinal blood flow starting with normals, then progressing to MCI and eventually AD. These findings could make the progression of AD detectable earlier in the course of its illness.


Conclusion.

It is not really surprising that both studies were of the retina. Any eye doctor could tell you that the retina is considered an extension of the brain. Both studies offer hope that AD may be detected or measured at very early stages with relatively simple non-invasive tests. More conclusive testing is warranted for both studies.

Metal Iron and Alzheimers

As alluded to in previous posts, amyloid protein plaques in the brain are strongly associated with Alzheimer's disease (AD).

A recent study at the University of Warwick found that several varieties of iron, especially an iron oxide called magnetite, combined with amyloid plaques in the brains of  people diagnosed with Alzheimer's. Plaques from the brains of two deceased patients were used in the study.

The study proposed that the interactions of iron and amyloid protein are responsible for the toxicity that leads to the death and/or the malfunction of brain cells. The understanding of the role of iron is exciting new information.

Dr. Joanna Collingwood, Associate Professor at the University of Warwick's School of Engineering commented: "Iron is an essential element in the brain, so it is critical to understand how its management is affected in Alzheimer's disease."  She further noted that this new finding opens the door to possible new treatments of  AD by the use of iron modifying drugs.

Dr. Collingwood was part of an international team that included researchers from University of Florida and The University of Texas at San Antonio.