Many neuro-degenerative diseases are a cause of aging. While memory loss is usually associated with neuro-degenerative diseases, it is, in fact, the cause of normal degeneration of the brain and formation of hard clusters of dying neurons, known as senile plaques; an increase in decayed dentricles - neuro-fibrillary tangles; and chemical interactions in the brain rather than the death of neurons. Long-term memory loss occurs in patients with neuro-degenerative disease long before the causes of the disease remotely reach the ability to kill brain cells.
One of the most devastating neuro-degenerative diseases in the United States today is Alzheimer's disease. “Alzheimer's is the eighth leading killer in the nation today,” explains Dr. Chris Gamblin, PhD, professor at the University of Kansas and project leader of The Role of Tau in Alzheimer's and Other Neuro-degenerative Disorders.
“About 20 to 30 million people today suffer from mild-cognitive impairment and about 70 percent of those 20 to 30 million will have at least a small case of Alzheimer's disease2.” Alzheimer's patients tend to live shortened lives caused by secondary effects of the disease. For example, a woman with Alzheimer's disease may lose her ability to swallow correctly and develops pneumonia from food entering the lungs, or a man with Alzheimer's disease loses control of his bladder, which leads to infection. Usually, Alzheimer's patients pass away from secondary causes of the disease about eight years after being diagnosed.
Gamblin says that, physically, Alzheimer's disease cannot be confirmed until death and an after an autopsy is performed2. Doctors diagnose Alzheimer's patients with the disease when the patient displays significant memory loss and one other cognitive disability such as movement, speech, change in behavior, problems performing routine tasks, disorientation, and poor judgment. After death, a doctor's diagnosis is confirmed by the presence of large quantity of senile plaque and neuro-fibrillary tangles in the micro-tubules of Alzheimer's patients.
While the cause of Alzheimer's disease is unknown, many scientists believe that the disease is caused by abnormally polymerized forms of the proteins beta-amyloid and tau2. For a century, Alzheimer's disease has been studied to determine the causes and effects of the disease on the brain. Until the early 1990's, before proteins tau and beta-amyloid were discovered to effect cognitive thought, little progress had been made.
Most research being done today regarding Alzheimer's deals with the effects of beta-amyloid on the formation of senile plaques in Alzheimer's patients. The majority of multi-million dollar researching institutes dealing with Alzheimer's and other neuro-degenerative disease focuses their research on the beta-amyloid protein. Therefore, smaller researching institutions develop research projects regarding the effects of tau protein. However, tau protein research may hold as much influence on the disease as beta-amyloid.
Dr. Chris Gamblin's team, a smaller researching institution, focuses its studies on the polymerization of tau proteins. Even though most people believe that the beta-amyloid protein has a greater effect on Alzheimer's, Gamblin reveals, “We cannot compete with multi-million dollar corporations researching beta-amyloid. Rather than working on the same research, we are more productive working on a smaller scale with tau protein. I believe that tau protein is leading us in the right direction. I agree that beta-amyloid does have an effect on Alzheimer's patients, but I believe the key to the problem lies with tau2.”
In a normally functioning human brain, tau is responsible for stabilizing the neuron in micro-tubule nerve cells. Micro-tubules provide transportation to the different parts of the cell. During normal function, tau merely keeps equilibrium within the cell. In an Alzheimer's patient, tau becomes hyperphosphorylated2 - large amounts of phosphates are introduced to the tau protein - and forms a neuro-fibrillary tangle called abnormally phosphorylated tau (PHFtau). The neuro-fibrillary tangles lose their ability to bind to molecules thus hindering the neurons ability to transfer signals through the cell body.
In a normal functioning neuron (top) tau upholds the micro-tubules in the cell. In a pathological neuron (bottom), the neuro-fibrillary tangles hinder the cells ability to support axonal transportation of molecules throughout the cell. Picture by Ann Thomson5
The research being in Dr. Gamblin's lab consists of monitoring the effects of the phosphorylation on the polymerization of tau. Polymerized tau protein forms the neuro-fibrillary tangles that turn normally functioning neurons into pathological neurons. Dr. Gamblin says, “Our research is interested in finding out how tau protein connects and polymerizes. If we could find the point at which tau proteins connect and remove this point, we believe we can stop the formation of hyper-phosphorylated tau protein2.”
(Picture by Roger Knowles' Lab7)
Green - Beta-amyloid peptide (forms senile plaques)
