Alzheimer's Fighting off Infections; Who Knew?

 
INTRODUCTION:

Recent research indicates that Alzheimer's can stem from the toxic remnants of the brain's attempt to fight off infections. Team of researchers from Harvard are close to finding the reason behind the origins of plaque tau found in individuals who suffer from Alzheimer's.

Experts on Alzheimer's disease are captivated by the idea that infections, those that are too mild to cause actual symptoms could possibly produce a fierce reaction leaving debris in the brain and in this case causing Alzheimer's in people as they age. The hypothesis makes sense and the data supports the hypothesis in that the major implications for preventing and treating this degenerative brain disease.

Dr. Michael W. Weiner is a radiology professor at University of California, San Francisco. He is the lead investigator of the Alzheimer’s Disease Neuroimaging Initiative where the goal of the organization is to create a large national effort to track the progression of the disease and look for biomarkers like blood proteins and brain imaging to signal the disease’s presence.

A virus, fungus, or a bacterium gets into the brain, passing through the the blood brain barrier membrane which becomes leakier with age. The brain’s defense system rushes in to stop the invader by making a sticky cage out of proteins, called beta amyloid. The microbe gets trapped, leaving behind a plaque that is the unique hallmark of Alzheimer’s. Data from the research, so far, have supported their hypothesis of the neurons growing in petri dishes including those in yeast, roundworms, fruit flies, and mice.

 

 

The origins of this idea and its work started with Robert Moir who had an idea about the function of amyloid proteins, normal brain proteins which have always been a mystery. The hypothesis has been that with age the brain accumulates 'garbage' that were called proteins by scientists. What Dr. Moir noticed that others didn't was that the proteins looked very similar to that of the innate immune system. What does this mean? The innate immune system is a primitive system that is the body's first line of defense against infections.

If these proteins were to be found anywhere else in the body, for example proteins called trap microbes ( viruses, fungi, yeast, bacteria). After the initial defense, the body releases WBCs to clear up any mess formed. Dr. Moir, came to the conclusion of the possibility that amyloids were also part of that system. AT Harvard Medical School and Massachusetts' General hospital, he began working with Rudolph Tanzi on a study to see if amyloids were trapped in microbes in living animals as well as if mice which lack these amyloid proteins were quickly ravaged by infections that amyloid could have stopped.

In a study where salmonella was injected in the bacteria in the brains of young mice that did not have plaques. Overnight, the bacteria gave birth to plaques. The hippocampus was full of plaques, and each plaque had a single bacterium at its center. Those that did not form beta amyloid plaques succumbed more quickly to the bacterial infection. Plaques never formed in their brains.

The idea in researchers minds has always been that the plaques were a form of trash accumulated in the brain. Alzheimer's pathway is supported by years of research. Plaques form and set off the formation of  tangled threadlike tau proteins. Then, as tangles of tau kill nerve cells, the brain becomes inflamed, resulting in the killing of many more nerve cells. There were a few puzzling clues that something else might be going on, but they did not make much sense.

Investigators have indeed reported that individuals who developed Alzheimer’s revealed to have higher levels of antibodies to herpes- an indication of a previous infection- compared to those who did not have the disease. Dr. Berislay Zlokovic's studies also support this statement. The blood brain barrier fits this hypothesis. He discovered that the barrier began degrading due after years of aging and of all the regions, the hippocampus (site of learning and memory) was the leakiest part of the membrane. Coincidentally, this is also where Alzheimer’s plaques form.

 

 

Then there are individuals who have a mutated gene that guarantees that they will eventually develop the disease at an early age. The problem here is that these individuals vastly overproduce beta amyloid. So much of these begin to clump up even without the presence of microbes. Uniquely enough, not everyone who has had a brain infection develops Alzheimers. Some individuals seem to be more vulnerable to the disease than others.

A new theory proposes that the brain has the ability to clear out balls of beta amyloid after they have killed the microbes. Individuals with the gene 'ApoE2' have brains that are skilled at clearing out this plaque subsequently lowering their risk of developing Alzheimer's in their later years. Then there are individuals who have different version of this gene which are inefficient in removing plaque and therefore have a high risk of developing Alzheimer's.

The incidence of dementia has been declining is the past few years. The reasoning behind the results of these recent data suggests that individuals have been taking better control of their blood pressures and cholesterol levels. By doing so, they are starving off mini strokes which can cause dementia. Much more work is needed in this area of medical research.

 

 

 

The Cure Alzheimer’s Fund is initiating a large collaborative project that will use gene sequencing technology to carefully look for microbes in the brain. These careful observations will range from the brains of people who had Alzheimer's and those who never developed the disease. The microbes located within the plaques in human brains will also be collected. Dr. Tanzi strongly suggests that the very first question that needs to be answered is whether there are microbes that can sneak into the brain as we age triggering amyloid deposition so that we can then set a new goal in stopping them.

Links:
(A)http://www.nytimes.com/2016/05/26/health/alzheimers-disease-infection.html?_r=0

*Please note! These images are not mine. They were found on various tumblr sites! If any are yours please let me know so that I can give you credit for them! Also the people in the images have no relation to the diseases, illnesses, or cancers I write about. Thanks so much & enjoy~

Asthma Drug: Rejuvenating Aging Brains

INTRODUCTION:

An anti-asthmetic drug was used in various trials with rats to determine its benefits on the aging brain. The inhibition of the leukotriene receptor signaling might be the key to restoring cognitive functions in older patients and those who have dementia.(A)

Scientists who have studied rats aim to begin similar trials on patients who have dementia from their discovery of an asthma drug which reduced brain inflammation as well as increasing neuron growth in their rats. According to these research findings, the drug that prevents asthma attacks could be the key to rejuvenating the aging process of the human brain. (B)

This drug is called 'montelukast' which improves memory and learning in older rodents whose performance matched those of younger animals in the cognitive tests performed.  In other words, it is a an anti-asthmatic drug that antagonizes leukotriene receptors which reduces neuronal inflammation, increases neurogenesis in the hippocamous, while improving memory and learning in older animals. This study demonstrated that through the inhibition of GPR17 receptor is mediated by using knockout gene approaches. (A)

The way in which montelukast works is through a combination of a decrease in brain inflammation and the growth of new neurons in the hippocampus. Although, performance of older rats improved the younger rats were not affected by the drug (in other words their performance did not improve but stayed the same). Now, the goal is to start clinical trails on patients with dementia. With age, the human brain functions decrease and can be clearly seen through symptoms of memory loss, decline in cognitive skills, decreased growth of formation of new brain cells, and gradual increase in inflammation of the brain. (B)

The reason as to why these scientists decided to research the affects of montelukast on the brain is because with patients who have asthma this inexpensive drug blocks inflammation. If this drug- that linked biological pathways to asthma- could decrease the various inflammatory conditions in the body, then there is a possibility that montelukast could perform the same functions and have the same affects on the human brain. (B)

RESEARCH:

Rats were given daily doses of montelukast. There were two age groups: four month old rats (equivalent to children/young adults in humans) to 20 month old rats( equivalent in age to 65-70 year old humans). Although the older rats did not have dementia, their brain functions showed a very similar decline as to those of older individual humans. Both groups of rats were trained to find within a pool a submerged platform. Once 5 days passed, the older rats were still uncertain about the location of the platform. Those that were given the drug, found the submerged platform almost as well as the younger rodents. (B)  

Two days were used as a break from training. Then, the next day the rats were lowered into the pool once more to look for the platform. The older animals had a difficult time remembering where the platform was. Those who were on the drug had better memory and found it almost as quickly as the younger animals. More tests were conducted to see how the rodents demeanor changed if familiar objects in their cages were moved from one place to another. The younger ones tended to spend more time observing the moved objects as did the older rats who were given the drug. The scientists linked this behavior to these rodents having better memory of the objects original positions. (B)

CONCLUSION: 

Results showed that the brains of the older rats that were on the drug had more new neurons and less inflammation than those who received the placebo.  The results of this study is very hopeful for those suffering from neurodegenerative diseases but more research has to be conducted in order for scientists to be sure of the benefits this drug will have on patients. (B)

 “The approach of repurposing existing drugs is a promising one as it could mean new treatments for dementia become available in half of the time of a standard drug - bringing hope to hundreds of thousands. Through our drug discovery program, Alzheimer’s Society is currently co-funding a clinical trial into the arthritis drug Etanercept, which could work in a similar way by reducing inflammation in the brain.(B)

Since life expectancy has increased, more and more age related cognitive illnesses have become more common. This represents a great challenge to physicians, researchers, and scientists alike to find cures for these chronic diseases and ways in which they can better treat individuals with such age related cognitive difficulties.

Links:
(A)http://www.nature.com/ncomms/2015/151027/ncomms9466/full/ncomms9466.html
(B) http://www.theguardian.com/science/2015/oct/27/asthma-drug-could-rejuvenate-ageing-brains-study-suggests

 *Please note! These images are not mine. They were found on various tumblr, pinterest, google image sites! If any are yours’ please let me know so that I can give you credit for them! Also the people in the images have no relation to the diseases, illnesses, or cancers I write about. Thanks so much & enjoy~ Screenshots by: google images