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Finding the Missing Link in Treating Alzheimer’s Disease

Megan Hayes | News Editor

Microglia (brain cells) and beta-amyloid proteins (orange), 2022. / NPR

Alzheimer’s disease is a heartbreaking illness that results in symptoms like memory loss, forgetfulness, disorientation, agitation and confusion. Typically, people over the age of 65 are more prone to experiencing Alzheimer’s disease, but it can also affect younger people, although it is very uncommon. Alzheimer’s disease is a progressive disease that, up until now, has been speculated to be typically caused by abnormal buildup of proteins in and around the brain (defined as amyloid plaques and neurofibrillary tangles), which cause neuro-inflammation. This disease causes progressive memory loss by injuring neurons around the brain, eventually causing the brain to shrink in volume (also called brain atrophy). While scientists still don’t know directly what causes the plaques and tangles of Alzheimer’s disease to develop, there is research going into how exactly family history, brain structure, diet and exercise, as well as many other factors play into the probability of being diagnosed with the disease. In this research, some scientists have discovered that plaques and tangles may not be the cause of the disease, which opens the possibility for effective treatment, as treatment has been unsuccessful. The disease has been labeled incurable, but these new results are a bridge to promising findings.

Alzheimer's, which is one of the main causes of dementia, has been placed into the hands of many scientists and researchers over the years, with many around the world begging for a cure. So far, within clinical trials, treatments focus on the amyloid beta plaques of the brain, and none have been successful thus far—so scientist Changjoon Justin Lee, Director of Center for Neuroscience at the Korea Institute of Science and Technology, started looking into alternate causes of the disease, looking in corners that no treatments have veered into before. Lee, along with his research team, have proposed a novel theory that we are looking in the wrong place, and that reactive astrocytes are the true cause of Alzheimer’s disease. Astrocytes, a type of glial cell in the brain, have a purpose of helping to hold nerve cells in place so that they can work properly without disruption. However, these astrocytes may become reactive due to uptake of elevated levels of acetates (trauma to the cell, like conditions of the nervous system, stroke, trauma, tumors, and many other causes), as according to News of Medical Life Sciences. Lee and his research team have discovered that these reactive astrocytes, as well as the proteins within them, could be used as an effective target for treatment of Alzheimer’s disease. The team is still working on ways to clearly see if treatment works, as Positron Emission Topography scans (PET), along with radioactive acetate and glucose probes are being used to clearly see the function of the astrocytes. PET scans, which typically show how organs and tissues are working, do not yet clearly show the specific function of the reactive astrocytes, which is why additional measures are being added on.

| "Reactive astrocytes showed metabolic abnormalities that excessively uptake acetate compared to normal state. We found that the acetate plays an important role in promoting astrocytic inflammatory responses." - Dr. Yun Mijin, author

Although Lee and other scientists grappling with this complicated but possibly revolutionary discovery will run into some roadblocks, the future of this new hypothesis looks extremely promising. With all other treatments and clinical trials having failed so far, it would make sense that the culprit of Alzheimer’s disease is hidden, and hasn’t been looked for up until now, when Lee’s proposal was released in early April of 2023. Future research into reactive astrocytes and astrogliosis (the condition of the cells becoming inflamed) as a result of them may help us to understand if there are ways to prevent Alzheimer’s and dementia, or the best course of action to take when someone is diagnosed. The researchers are looking at acetate, the main component of vinegar found in the brain, as the cause of kickstarting astrogliosis, and production of putrescine and GABA, two chemicals in the brain which cause dementia. As stated before, this research is still in the very infantile stages of getting recognition and will next undergo trials to prove its viability to the scientific communities struggle to cure Alzheimer’s disease.


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