Thanks Lane for this great find on microglia. I found the 2009 Medscape article about Dr Streit's research very informing, and based on the research by Dr Streit and also by Dr Ludwig Aigner and their teams, I can see the importance of microglia in the the progression of Alzheimer's and other dementias.
According to Wikipedia, microglia are resident macrophage cells, acting as the first and main form of active immune defense in the central nervous system (CNS). Microglia are widely distributed in the CNS and make up 10 to 15% of all cells found in the brain. Microglia are key cells in overall brain maintenance - constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Damage to the microglia would result in serious injury to the brain.
In Dr Streit's 2009 research on microglia, he and his colleagues obtained 19 specimens from the brain bank at the Institute for Clinical Neuroanatomy at the University of Frankfurt, Germany. The specimens represented a range of pathologies from no AD to severe AD.
The hypothesis at the time was that amyloid deposits in the brain trigger an inflammatory reaction. According to this theory, the inflammatory response activates microglial cells to produce toxic substances that in turn cause neurons to degenerate. But when he looked in the areas next to destroyed neurons in the AD specimens, he couldn't find any activated microglial cells. What he found was microglial cells that had broken apart, fragmenting into many small pieces. Therefore he concluded that AD is linked to microglia degeneration. He didn't adequately explain the reason for the degeneration. He also stated that because that he could not find activated microglia, inflammation is not a major factor. I think he was wrong on that interpretation. The microglia could have become activated at an earlier stage, causing inflammation, and then become exhausted and fragmented at a later stage of AD.
He also stated that many studies had failed to show that anti-inflammatory drugs could have a positive affect in the treatment of AD. I believe he was referring to studies of Non-steroidal anti-inflammatory drugs (NSAIDs) during that time period. Numerous studies showed then that they did not work. However there are other classes of anti-inflammatory drugs that were not studied as AD treatments at the time of his research.
Moving on to Dr Ludwig Aigner's research in 2015, he and his team examined the brains of young and old rats treated with montelukast. One group of young rats was untreated. Another group had montelukast added to its food for 6 weeks. One group of old rats was untreated. Another group of old rats also had montelukast added to their food for 6 weeks. Montelukast (Singulair) is a generic drug approved for the treatment of asthma. Within the brain, the drug blocks cysteinyl leukotrienes, inflammatory substances secreted by microglia, from entering nearby brain cells.
The brains of the young rats not treated showed no signs of inflammation or microglia activation. The brains of the old rats not treated showed signs of inflammation, and in particular, microglia activation with soma enlargement (the soma is the bulbous part of the cell containing the nucleus). The brains of the old rats treated with montelukast had microglia with normal size soma and reduced inflammation.
My theory is that microglia can become activated causing chronic inflammation in the earlier stages of dementia and over the years the microglia can become exhausted and break up, leaving the brain unable to keep up with maintenance and defend itself from outside agents. Montelukast appeared to reverse the activation.
So why in Dr Aigner's research did the activated microglia in the old rats not break up. My theory on this is that rats have a short life span compared to humans. Therefore they will never live long enough for the microglia to break up after chronic activation.
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