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

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Hidden Figures: Dementia

 Dementia:

Not a specific disease, dementia, is a group of conditions characterized by the impairment of at least two brain functions, such as memory loss and judgment. Symptoms include forgetfulness, limited social skills, and thinking abilities so impaired that it interferes with daily functioning. Medications and therapies may help manage symptoms. Some causes are reversible. A group of thinking and social symptoms that interferes with daily functioning. Affecting more than 3 million lives in America alone, dementia is very common. It can be chronic, lasting for years or be a lifelong condition. Unfortunately, it can not be cured, but treatments can help.

Alzheimer's Disease:

This is the most common form of dementia that is seen in patients. It is considered a slow progressive brain disease that begins before symptoms even emerge. Roughly about 60 to 80 percent develop Alzheimer's Disease. Early symptoms of individuals struggling with Alzheimer's Disease include having trouble remembering recent conversations, names, or events as well as apathy and depression. As the disease progresses with time, so do the symptoms. Communication is impaired, there is poor judgement, disorientation, confusion, behavior changes, and difficulty speaking, walking, and swallowing. The brain is altered from the deposits of protein fragment Beta-Amyloid Plaques, twisted strands of tau proteins (tangles), nerve cell damage, and cell death in the brain. 

Vascular dementia:

Previously known as multi-infarct or post-stroke dementia, vascular dementia is less common as a sole cause of dementia than Alzheimer’s, accounting for about 10 percent of dementia cases. Individuals have impaired judgement or inability to make conscious decisions. They are unable to plan or organize is usually the first symptoms of Vascular Dementia compared to that of Alzheimer's where the individual has memory loss as their initial symptoms. The reason why people suffering with VD have trouble making decisions is because of the blockage of blood vessels or brain damage that causes strokes or bleeding in the brain. The location, number and size of the brain injury determines how the individual's thinking and physical functioning are affected.

Brain imaging can often detect blood vessel problems implicated in vascular dementia. In the past, evidence for vascular dementia was used to exclude a diagnosis of Alzheimer's disease (and vice versa). That practice is no longer considered consistent with pathologic evidence, which shows that the brain changes of several types of dementia can be present simultaneously. When any two or more types of dementia are present at the same time, the individual is considered to have "mixed dementia" (see entry below).

Dementia with Lewy Bodies (DLB):

People with dementia with Lewy bodies often have memory loss and thinking problems common in Alzheimer's, but are more likely than people with Alzheimer's to have initial or early symptoms such as sleep disturbances, well-formed visual hallucinations, and slowness, gait imbalance or other parkinsonian movement features. Lewy bodies are abnormal aggregations (or clumps) of the protein alpha-synuclein. When they develop in a part of the brain called the cortex, dementia can result. Alpha-synuclein also aggregates in the brains of people with Parkinson's disease, but the aggregates may appear in a pattern that is different from dementia with Lewy bodies. The brain changes of dementia with Lewy bodies alone can cause dementia, or they can be present at the same time as the brain changes of Alzheimer's disease and/or vascular dementia, with each abnormality contributing to the development of dementia. When this happens, the individual is said to have "mixed dementia."

Mixed Dementia:

In mixed dementia abnormalities linked to more than one cause of dementia occur simultaneously in the brain. Recent studies suggest that mixed dementia is more common than previously thought. Characterized by the hallmark abnormalities of more than one cause of dementia —most commonly, Alzheimer's and vascular dementia, but also other types, such as dementia with Lewy bodies. As Parkinson's disease progresses, it often results in a progressive dementia similar to dementia with Lewy bodies or Alzheimer's. Problems with movement are common symptoms of the disease. If dementia develops, symptoms are often similar to dementia with Lewy bodies. Alpha-synuclein clumps are likely to begin in an area deep in the brain called the substantia nigra. These clumps are thought to cause degeneration of the nerve cells that produce dopamine.

 Frontotemporal Dementia : 

Includes dementias such as behavioral variant FTD (bvFTD), primary progressive aphasia, Pick's disease, corticobasal degeneration and progressive supranuclear palsy. Typical symptoms include changes in personality and behavior and difficulty with language. Nerve cells in the front and side regions of the brain are especially affected. No distinguishing microscopic abnormality is linked to all cases. People with FTD generally develop symptoms at a younger age (at about age 60) and survive for fewer years than those with Alzheimer's.

 CJD or Creutzfeldt-Jakob Disease:

CJD is the most common human form of a group of rare, fatal brain disorders affecting people and certain other mammals. Variant CJD (“mad cow disease”) occurs in cattle, and has been transmitted to people under certain circumstances. Rapidly fatal disorder that impairs memory and coordination and causes behavior changes. Results from misfolded prion protein that causes a "domino effect" in which prion protein throughout the brain misfolds and thus malfunctions.

 

Normal Pressure Hydrocephalus:

Symptoms include difficulty walking, memory loss and inability to control urination. Caused by the buildup of fluid in the brain. Can sometimes be corrected with surgical installation of a shunt in the brain to drain excess fluid.

 Huntington’s disease:

This progressive brain disorder caused by a single defective gene on chromosome 4. Include abnormal involuntary movements, a severe decline in thinking and reasoning skills, and irritability, depression and other mood changes. The gene defect causes abnormalities in a brain protein that, over time, lead to worsening symptoms.

Wernicke- Korsakoff syndrome:

Chronic memory disorder that is caused by severe deficiency of thiamine (vitamin B-1). The most common cause is alcohol misuse. Memory problems may be strikingly severe while other thinking and social skills seem relatively unaffected. Thiamine helps brain cells produce energy from sugar. When thiamine levels fall too low, brain cells cannot generate enough energy to function properly.

Research:

Researchers of University of Leicester conducted a study where they observed and recorded the ways in which lower levels of toxic by-products were produced by the nervous system of fruit flies. These fruit flies were previously engineered to have beta amyloid plaque build ups which causes neurodegeneration. Neurodegeneration negatively affects crawling and climbing abilities of these flies and shortened their lifespans. The collected data from the study showed that by lowering the levels of toxic metabolites (aka: the by-products of biological processes in the nervous system of the flies) can have a neuroprotective effect. (B)

Dr Doug Brown, Director of Research and Development at Alzheimer’s Society, said:

'Studies in fruit flies can help us to better understand some of the underlying biological changes that happen in Alzheimer’s disease. However, they only represent a very simplistic version of the condition – behavioural changes seen in fruit flies, such as slow crawling and climbing, are very different from the symptoms people with Alzheimer’s disease experience.(B)

Each year, roughly about 200,000 individuals will be diagnosed with dementia and the last time there was a new treatment presented to the public for patients with Alzheimer's disease was in 2002. So it is important that more research is being conducted so that people being diagnosed for dementia or those living with dementia can live more functioning and manageable lives. (B)

Alzheimer's Society is now uniting the Medical Research Council with the Alzheimer's UK Research team to tackle dementia thanks to a 50 million euro investment. The Prime Minister hopes to bring together scientists and experts from across the globe to transform the landscape of dementia research. The aim is to establish the very first Dementia Research Institute in the UK and to secure UK's reputation as the world leader in research and development against dementia. He call's it his 'Challenge on Dementia 2020'. Their government even invested £150 million to success of the program. (C)

The focus of this program will be to have a network of regional centers where hundreds of researchers will be able to interact with each other so that innovative scientific discoveries can be made more frequently that will help people world wide. The discovery of the mechanisms of the development and progression of dementia will improve health care strategies and improve care while reducing the risk of dementia for future generations. (C)

Links:
(A)http://www.theguardian.com/commentisfree/2016/feb/29/secret-life-dementia-sufferer-carer-iron-fridge
(B)https://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=2595
(C)https://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=2598

*Please note! These are not my images! If any are yours please let me know so that I can give you credit for them~ Also these images have no relation whatsoever between the people in these images and the Diseases I am discussing about. Thanks so much~ Enjoy!