To this day, scientists still don’t have a definitive, single cause for Alzheimer’s, the most common form of dementia. As a result, the predominant form therapy takes is the treating of the symptoms as and when they manifest. Naturally this limits how effective treatment can be, given by the time symptoms manifest it is often too late to reverse any damage that has already been done. But some researchers at Yale University may have identified a new avenue therapy can take to drastically improve a patient’s quality of life for an extended period.
Researchers have known for a while that most Alzheimer’s patients show a build up of a substance called amyloid plaque in their brains1. It isn’t a rule that this substance will be present in every single patient, but its occurrence is significant enough to warrant study. Amyloid plaque can be understood as a build up of misfolded proteins that occur when a larger protein is broken down. This amyloid plaque forms in the spaces between nerves in the brain and begins to clump around the neurons. The presence of the plaque then leads to swelling along the nearby axions, the super fine connections between the neurons2. This swelling then appears to blunt the electrical signals being transmitted along the axions, which can lead to some of the symptoms of Alzheimer’s.
Knowing this, scientists have been working on drugs to combat the buildup of plaque in hopes of minimizing its impact on the patient, however up till now these trials have been met with mixed results. But a new approach may show promise. When the body encounters a problematic substance or some such anomaly, it releases its defenses. One such defense is lysosomes, which are organelles within cells responsible for the digestion of cellular waste3. As we age, all the various processes of our body unfortunately become less effective, including our bodies defenses. As a result, when lysosomes arrive to break down the plaque, they aren’t able to filter out appropriately and build up around the axions. It’s this accumulation of lysosomes that leads to the aforementioned swelling.
Further research into the lysosomes of Alzheimer’s patients has revealed that they contain a protein called PLD3, which is what causes them to clump together. Trials done in mice that exhibit a condition similar to Alzheimer’s, found that using gene therapy to remove the PLD3 protein from the lysosomes caused the axonal swelling to drastically reduce, which led to the neurons regaining much of their previous efficacy. This means we could begin to use the presence of PLD3 as a biomarker in patients and aim our therapies at addressing its presence rather than only dealing with the amyloid plaque build-up; meaning while the plaque may be the root cause of the degradation of these neural pathways, we can potentially reduce the effect of its presence for an extended period.
The next step for these researchers will be to further explore the relationship between PLD3 and Alzheimer’s, as well as explore other molecules that have a role in lysosomal regulation. This new discovery opens up many new paths to explore as we try to find both the cause of Alzheimer’s as well as an effective cure for the disease that has such a massive impact on our society. Keep an eye on this blog going forward, as we’ll be sure to keep you updated and in the loop.
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