By Talia Beechick
When you hear the word “protein,” what springs to mind? A bodybuilder rippling with muscle? A hearty steak fresh off of the grill? What about disease? It turns out simple, destructive proteins are behind some of the most intractable diseases today, diseases like Alzheimer’s.
What Can Cause Alzheimer’s Disease?
Researchers have linked the “tangling” of proteins in the brain to the development and progression of Alzheimer’s as well as other neurodegenerative diseases. The “tau” protein is usually a positive force in brain function and in memory processes but can begin to cluster in neuron filaments (forming tau tangles) with old age, causing an onset of Alzheimer’s disease. Scientists at Beth Israel Deaconess Medical Center in Boston (BIDMC), funded with grants from the National Institutes of Health, have developed an exciting new antibody technology to distinguish between the positive and negative tau proteins and even remove the destructive ones entirely. They are hoping this new method of detecting the disease at an earlier stage will aid in reducing and even preventing the onset of Alzheimer’s altogether.
Tau Protein Explained
So let’s start from square one: what is this “tau protein” and why does it undergo such a radical transformation? Typically, the tau protein participates in not only the normal functioning of the brain, but also memory processing; it assembles and supports the microtubules which give neurons their unique shape. As part of this process, phosphates of two different shapes, or isoforms, are added onto and removed from the tau protein: the trans isoform, which is in a relaxed shape, and the cis isoform, which maintains a twisted shape. This process is known as phosphorylation, and any abnormalities or interruptions within this plays a large role in the development of Alzheimer’s.
In 1995, an enzyme called Pin 1 (prolyl isomerase) was discovered by Dr. Kun Ping Lu of the BIDMC and professor of medicine at Harvard Medical School, and Dr. Tony Hunter, of the Salk Institute for Biological Studies. Pin 1 protects against the onset of Alzheimer’s; it has the ability to untwist the cis isoform and return it to its relaxed position, thereby completing the phosphorylation process. Lu and a team of scientists created a group of protein fragments to mimic the tau shapes as antigens to generate antibodies, using this new tool to analyze tissue samples from both healthy brains and the brains of Alzheimer’s patients in varying stages of the disease.
They then discovered the twisted cis tau in early dementia patients which developed to Alzheimer’s as the cis isoform accumulated and became tangled in the diseased neurons. They seemingly clustered at locations which would affect memory; the trans isoform, however, did not appear in the patients whatsoever. Scientists then tested to see the impact of the Pin 1 enzyme on this process and, sure enough, increasing the levels of Pin 1 prevented this tangling, whereas reducing the enzyme led to the creation of these destructive knots.
Researchers are hopeful that this discovery will allow them to identify the villainous tau in patients and then treat them accordingly with antibiotics or vaccines. Lu stresses the importance of patients receiving treatment in the early stages of the disease in order to prevent further memory loss, and claims that identifying the period in which the tau protein is transformed from a positive force to a negative one is crucial in overcoming Alzheimer’s. He continues by explaining that, through their new, innovative approach to create antibodies, they will be able to remove the disease-causing tau and leave the healthy proteins in order to continue functioning properly.
Dr. Tony Hunter emphasizes the importance of this discovery, suggesting that scientists are aware that only one of the tau isoforms is present in Alzheimer’s affected tissue, the newly created antibodies could be transformed into a kind of therapy. Using them to analyze cerebrospinal fluids, for example, would allow scientists to diagnose the onset of the disease and even predict its severity.
Alzheimer’s accounts for a majority of dementia cases and causes issues with memory, thinking and behavior in victims. Symptoms typically develop slowly and progressively get worse over time, usually affecting individuals over 60 years of age. In its beginning stages, Alzheimer’s negatively affects one’s ability to remember newly processed or learned information; the disease usually gets progressively worse over time, however, and can lead to other symptoms, such as disorientation, suspicions about family, mood and behavior changes, more serious memory loss, difficult speaking, swallowing and walking, and confusion about the time and place of events.
Dr. Barry Reisberg, clinical director of the New York University School of Medicine’s Silberstein Aging and Dementia Research Center, developed seven stages of Alzheimer’s, ranging from no impairment to mild cognitive decline, moderately severe cognitive decline to late-stage Alzheimer’s disease. In this final, seventh stage, individuals lose the capability of responding to their environment, holding a conversation and controlling movement.
There are 5.4 million Americans currently suffering from some severity of Alzheimer’s disease, and researchers are predicting that number will skyrocket to 16 million by 2050, which is 120 million people worldwide. It is the sixth leading cause of death in the United States and it also is the only top 10 cause of death which, up until recently, scientists have been unable to cure, prevent or even slow. Although death rates declined from 2000-2008 for several major diseases including heart disease, breast cancer, stroke and HIV/AIDS, the death rate for those with Alzheimer’s has risen by 66 percent in that same range of years.
Although it has been considered incurable since German psychiatrist and neuropathologist Alois Alzheimer first described it in 1906, Alzheimer’s may finally come to be a treatable disease in the near future. Due to their new antibody technology, researchers at BIDMC are hopeful for further progress in both the reduction and prevention of this disease. You can visit the BIDMC website for further information and updates: http://www.bidmc.org.