Alzheimer’s disease is a progressive disorder that causes brain cells to degenerate and die. This disease is the number one cause of dementia- a continuous decline in thinking, behavioral and social skills that disrupts a person’s ability to function independently. The early signs of the disease may be forgetting recent events or conversations and not being able to perform daily functions. As the disease progresses, a person with Alzheimer’s disease will develop severe memory impairment and lose the ability to consistently carry out everyday tasks. It is most prevalent among people of old age but can be diagnosed in people of all ages. There is no current cure, but treatments for symptoms are available and scientists are continuing to research. Ever since the first case of this disease was diagnosed over a 100 years ago, scientists always believed that it is caused by plaques and tangles in the brain. But a University of California, Riverside, research team led by Ryan R. Julian has identified alternate chemistry that could account for the various problems associated with the disease.
(Plaque storage in the brain)
As mentioned in the last paragraph, plaques and tangles have been the main focus of this disease. Plaques are deposits of a protein fragment called beta-amyloid that clump up in the space between neurons. Tangle are twisted fibers of another protein, Tau that build up inside cells. This theory has been around for a long time but has never been proven by a clinical trial. So, the scientists at UC Riverside decided to figure out if this was really the cause and see if there was more to the causes. While researching, they were able to make an important connection. They examined a different disease known as Lysosomal Storage Disorder as they thought it to have similar causes and effects on the structure and function brain. While looking at both these diseases jointly, they found that lysosomal storage is also a cause of Alzheimer’s.
The Lysosome is an organelle in the cells of our bodies which is responsible for breaking down old proteins and lipids back to their monomer(building block) form. This is important because the synthesis of proteins is balanced by this degeneration of proteins. There is, however, a defect in this organelle. If the macromolecules that get sent there cannot be broken down, they stay in the lysosome which then causes the lysosome to be pushed to the side and the cell forms a new one. If the new lysosome fails, the process keeps repeating, resulting in lysosome storage.
(Cycle of Protein synthesis and degradation)
While researching more about the lysosome, Julian and his team also found evidence for the fact that long-lived proteins can undergo spontaneous modifications that can make them undigestible by the lysosomes. These proteins are formed by plaque and tangle and stay long in the body. Over time, changes occur in the fundamental structure of the amino acids in proteins, causing their structure and chemical makeup to modify. As a result, enzymes that ordinarily break down the protein in the lysosome are not able to do so because they are unable to latch onto the protein. “Long-lived proteins become more problematic as we age and could account for the lysosomal storage seen in Alzheimer’s, an age-related disease,” Julian said.
It was long known that proteins are chemically modified over time, but scientists in the past completely overlooked the fact that it could prevent the lysosome from performing its regular functions. “The proteins undergo this chemistry that is almost invisible, which may explain why researchers have not paid attention to it,” Julian says. One way to prevent this lysosome storage would be to recycle the proteins to re-stimulate a balanced flow of synthesized and decomposed proteins so that they aren’t sitting around long to go through these modifications. This process is called Autophagy. Researchers are now working on devising a drug that can perform this task as they hope to come up with a permanent cure for this disease.