Promising Developments for Future Alzheimer’s Research

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Issue 15, Volume 110

By Daniel Gordon 

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The first thing that comes to mind when hearing the word “Alzheimer’s” is likely an image of an elderly person struggling to remember his name. The unfortunate truth, however, is that the brain disorder, which can be diagnosed as early as 30 years old, affects much more than a person’s memory. As Alzheimer’s disease progresses, it strips away communication capabilities between neurons, or nerve cells, and induces neurodegeneration, or the accelerated loss of neuron structure and function. At the same time, parts of the brain that are responsible for memory and thought processing, among other cognitive functions, are destroyed. Even more devastating is that the damage done by Alzheimer’s disease is irreversible: the shriveling of several important important parts of the brain, such as the hippocampus—which regulates motivation, emotion, learning, and memory—is permanent. The permanence is due to the fact that neurons are one of the only cell types that never divide, so damaged cells cannot be replaced by healthy ones. Once neuron count in a person declines, it can never recover.

Since the first description of an Alzheimer’s patient was presented by German physician Alois Alzheimer in 1906, hundreds of thousands of studies have been devoted to finding treatments, cures, and new information about the human body’s most complex organ, the brain. Many advances have been made, including the ability to identify Alzheimer’s disease at an earlier age and to screen the brain for specific abnormal structures. Nevertheless, more than a century after the disease’s discovery, effective cures and reversible treatments are non-existent. The issue at hand isn’t that inadequate research has been put into the disease, but rather that scientists have been spending too much time on probable dead-ends instead of promising areas that may contain necessary clues to the problem.

One of the possible dead-ends that scientists continue to look into regards the function of the beta-amyloid protein fragment. Currently, a large amount of data supports the notion that the structure has a key role in the disease’s progression, and several drugs have been developed to reduce concentrations of it in Alzheimer’s patients. However, clinical trials have shown that these drugs do not stop the decline of cognitive functions in patients; in other words, the reduction of beta-amyloid in patients does not slow the decline of cognition, which contradicts the previous hypothesis that it does. A conclusion from the results of the clinical trials is that deeper knowledge of how Alzheimer’s disease develops and progresses is necessary to correctly assess whether inhibiting beta-amyloid has the potential to treat the disease. As such, researchers must look to other areas for the crucial information that they need to solve the puzzle.

A promising research path involves steps to better understand why the protein-disposal mechanisms in Alzheimer’s patients are different from those in healthy individuals. It is known that clumps of deformed proteins exist in the brains of Alzheimer’s patients; some clumps consist of beta-amyloid proteins and are found between neurons, while other clumps consist of tau proteins—which regulate important functional processes in neurons—and reside within neurons. What remains unclear to scientists is why the removal of protein clumps fails in Alzheimer’s patients. Recent findings from researchers at the Washington University at St. Louis and other institutions indicate that the abnormal proteins may evade the detection systems of cells by finding their way out of the cells. However, it remains unclear as to how the deformed proteins are capable of bypassing the natural defense systems.

A particular finding that expands current understanding of protein evasion is that tau protein can travel out of neurons and into the spaces between them before moving into neighboring cells. The purpose of such movement is unknown, but several implications have been suggested. One interesting speculation is that tau protein can be intercepted and cleared by antibodies when it is present outside of cells. Though this approach sounds reasonable, it is unlikely to work unless researchers discover the exact structure of misshapen tau that is necessary for the designing of a highly specific antibody. In addition, in order for this approach to work more efficiently, scientists must figure out where tau protein resides in the spaces between cells. Another approach involves uncovering how tau protein is released from cells and what receptors are used by neighboring cells to pick up the free tau.

Answers to the multitude of open questions can be found in the details of protein-disposal systems. Researchers need to examine both the mechanisms behind protein degradation in multiple subtypes of neurons in the brain as well as the foundation that the disposal systems use to identify and target misshapen proteins. Malformations in proteins develop in several steps, and it is yet to be uncovered at which step the disposal systems first recognize a changing protein as irregular. Knowledge about this identification process could lead to new strategies for testing treatments using drug intervention.

Today, over 600 clinical trials are being performed, each one having the potential to uncover crucial evidence for working treatments. In order for the future of Alzheimer’s research to advance more efficiently than it ever has, school education systems must start to employ a larger variety of lessons and programs that discuss mental health problems, like dementia. High school students should take greater interest in assisting in research laboratories and learning about Alzheimer’s disease-related content to contribute to ongoing studies. Additional support can only hasten the process of understanding enough about the brain to make that long-awaited leap to an effective treatment. It’s never too early to make a difference because, after all, the students of today become the scientists of tomorrow.