THE ROLE OF INFLAMMATION IN ALZHEIMER’S DISEASE

by Women's Brain Health Initiative:Alzheimer's disease (AD), the most common form of dementia, is characterized by two abnormal structures found in the brain--amyloid beta (Aß) plaques and tau protein tangles--as well as inflammation. Inflammation is the body’s response to injury - it works positively to heal wounds, but it can also have a negative impact in some chronic diseases, Alzheimer’s being one of them.Much research has focused on the structural changes involved in Alzheimer’s disease (i.e. the plaques and tangles). The amyloid hypothesis suggests that the accumulation of Aß triggers a cascade of neurochemical events that negatively impact the functioning of brain neurons and synapses, leading to cognitive decline. If the amyloid hypothesis were accurate, one would expect clinical treatments targeting the elimination of Aß to be successful at addressing symptoms and/or reversing the condition, but that has not been the case.Furthermore, some believe that the current drug treatments available are being administered too late in the pathology of the disease to be effective. According to Mark E. McCaulley and Kira A. Grush (in their 2015 article “Alzheimer’s Disease: Exploring the Role of Inflammation and Implications for Treatment” published in International Journal of Alzheimer’s Disease), “so far, anti-Aß clinical efforts have largely failed to meet primary clinical endpoints and, in some cases, have actually worsened dementia.”Research has confirmed there is a relationship of some kind between Alzheimer’s disease and Aß plaques, but the exact nature of that relationship is uncertain. It’s possible that it’s not a causal relationship; in other words, perhaps the amyloid hypothesis is incorrect and Aß accumulation does not begin the cascade of events in the brain leading to Alzheimer’s disease. McCaulley and Grush describe how some of the promising research is now pointing to a different potential causal factor, inflammation.It is clear that an inflammatory process is occurring in the brains of people with Alzheimer’s disease because activated microglia are seen in their brains. Microglia are the brain’s primary immune cells. They respond to ‘invaders’ (such as AD plaques and tangles) and injury by becoming activated - proliferating in numbers and migrating to the site of infection or injury then destroying any invading pathogens and removing damaged cells.Friend or Foe?Short-term inflammation is generally positive. When inflammation does its job properly, it deals with the invading foreign bodies that shouldn’t be there and then the inflammatory process ends. In the case of the Alzheimer’s brain though, ongoing deposition of Aß registers as constant detection of an ‘invader,’ and so the inflammation process becomes chronic, continuing without resolution.When inflammation becomes chronic, it appears that microglia do their job with such enthusiasm that they may be causing harm to healthy cells, leading to controversy in the scientific community around whether microglia are friend or foe to the brain.The idea that inflammation is an immune response to the presence of Aß is likely true. But research indicates that the relationship between inflammation and AD plaques and tangles is probably more complex than that. The latest research (published in the journal Brain in January 2016) supports the notion that inflammation in the brain may not be caused by the disease but instead could be driving the disorder. Researchers at the University of Southampton, England, in an experiment with mice bred to develop features of Alzheimer’s disease, discovered that blocking the receptor responsible for regulating microglia (CSF1R) resulted in fewer memory and behavioural problems in the treated mice.Overall, the research findings suggest that by reducing the inflammation, progression of AD could be halted. The research team is hopeful that the findings will lead to an effective new treatment for Alzheimer’s disease, although it will be critical to work closely with industry partners to find a safe drug that can be tested in humans.Other research supports the possibility that treatments aimed at reducing inflammation may be effective at reducing the risk of Alzheimer’s disease. Because non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are commonly used in modern societies, they have been evaluated for their potential influence on AD.The studies have mostly suggested a positive impact. A 2003 analysis of multiple studies of NSAID impacts on Alzheimer’s disease risk, published in the British Medical Journal, reported that longer-term use of NSAIDs (24+ months) was associated with a 73 percent reduction in AD incidence. It is important to note, however, that research findings have not all been positive with regard to NSAIDs. In some patients, the drugs made their symptoms worse. The benefits seem to be limited to people who have not yet developed more severe AD.The inflammatory mechanisms involved in Alzheimer’s disease are complex, making it challenging to develop appropriate therapies. Given the critical role short-term inflammation has in keeping your entire body healthy, simply suppressingthe inflammation process may result in more harm than good.More research is needed to fully understand the role of inflammation in AD, and to figure out how to target negative inflammation processes without “turning off” critical functions.Causes of InflammationThere are many causes of inflammation, many of which have been linked to increased risk of AD. In some cases, these causesof inflammation can be avoided or addressed — sometimes with non-pharmaceutical interventions.1     Moderate and severe traumatic brain injuries are obvious triggers of brain inflammation and have been linked to an increased risk of developing Alzheimer’s disease or other types of dementia.To avoid or address: Wear a helmet or other protective gear when engaged in activities such as cycling, in-line skating, playing hockey. Always wear your seatbelt in the car and avoid falls by using handrails on stairs and using a cane or walker if you need one.2   Certain foods can cause inflammation and may increase the risk of developing dementia, while other foods may be anti-inflammatory and possibly boost cognitive function.To avoid or address: Stay away from sugar, white flour products and processed foods. Some of the foods to embrace include leafy green vegetables, salmon and other cold-water fish, berries, extra virgin olive oil, and cold-pressed virgin coconut oil. For more about healthy eating for vibrant brain health, see the article “Millennials Have The Power To Prevent Their Own Cognitive Decline” or visit memorymorsels.org.3   While the exact nature of the association is unclear, there are conclusive links between depression, inflammation and dementia. Chronic inflammatory changes are known to be a common feature of depression, and evidence shows that depression often precedes AD and may be an early sign of dementia.To avoid or address: Although there is not definitive proof at this point that treating depression will decrease dementia risk, some research raises hope that may be the case, so be sure to seek treatment for depressive symptoms as a potential preventive measure.Other Possible Causes:Two additional causes of inflammation currently being researched, with no specific response measurements, include viruses and air pollution.Viruses such as Herpes Simplex Virus 1 (HSV-1) and HIV are known to affect the brain, causing inflammation and possibly contributing to increased risk of cognitive decline and dementia. Research to date on HSV-1 and Alzheimer’s disease has revealed only a correlation between the two, meaning that links have been found but there is no proof of a causal relationship.Some studies of older adults with active Herpes Simplex Virus 1 infections have shown those individuals are more likely to be diagnosed with Alzheimer’s than those without an active HSV infection, but it is not known why this happens and it certainly is not to be interpreted as proof that HSV causes AD.It’s possible the correlative relationship is coincidental, or that there are other risk factors not-yet-discovered that explain the link. HSV-1 is far more common than AD, so it’s obvious that HSV-1 could only be one of many factors than increase risk. Some estimates indicate that 80 percent of the population in the United States has HSV-1.Research suggests that tiny particles in air pollution also play a role in brain diseases. Studies have found that people who have been exposed to more air pollution, especially fine particles, are at increased risk for dementia and mild cognitive impairment.The fine and ultrafine particles in air pollution are able to travel from our nostrils directly into our brains, and although the research is in the early stages, it appears that these particles in the brain may be kicking off or accelerating brain degeneration.The presence of these small particles creates an inflammatory response in the brain; microglia are activated to deal with the invading particles. The toxins which are sometimes attached to particles can corrupt the microglia, putting them into a permanent attack mode, creating chronic inflammation.Source: http://bit.ly/MOMMag3