Archive for June, 2011

One of the distinguishing characteristics of Alzheimer’s disease (AD) is the destruction of brain cells that lead to diminished brain function. Scientists from the University of California at Santa Barbara have discovered what actually happens to these cells in patients with Alzheimer’s and other types of dementia. The findings of the study have been published in The Journal of Biological Chemistry online version.

According to senior author Stuart Feinstein, Ph.D, co-director of UCSB’s Neuroscience Research Institute, brain cells (also known as neurons) stop working properly. Neurons are essential for an individual to perform cognitive skills. The loss of neuronal capacity signals the onset of dementia.

Feinstein, a Molecular, Cellular and Developmental Biology professor, had spent 30 years studying the ‘tau’ protein utilizing cultured cells and test tube bio-chemistry models. Tau is present in long axons which are responsible for connecting neurons and their specific targets. Tau proteins also stabilize microtubules, a component of the cells’ cytoskeleton which is critical to the function and structure of neuronal cells.

For years, it was known that amyloid beta, a type of peptide, can cause the death of neuronal cells and lead to Alzheimer’s disease. The only problem is that it has never been understood how the mechanism that triggers it works. Recent research has shown that amyloid beta requires tau in order to destroy neurons. What is not clear is how it does the action. Most researchers believe that it triggers the excessive chemical modification of tau proteins. For Feinstein, the important goal was to discover the exact details involved in the process of abnormal phosphorylation. By determining what exactly happens, drug companies would have sufficient clues to make the right decisions and pharmaceutical solutions for the problem.

But there is a glitch. The initial hypothesis regarding the effect of amyloid beta on tau phosphorylation was incorrect. What the team discovered was that taking neuronal cells and adding amyloid beta did not result in massively phosphorylated tau proteins. Instead, it resulted in the fragmentation of the proteins within one to two hours and the death of the cells within 24 hours.

According to Feinstein, tau performs multiple jobs, the most widely understood of which is the regulation of cellular cytoskeleton. Cell skeletons, unlike human skeletons, do not undergo abrupt change in its shape. Cell skeletons constantly move, grow and shorten to allow the cell to perform its many functions. The length of cytoskeleton is essential to neurons due to its length.

After the findings, Feinstein’s argument is that the death of neurons that occur in Alzheimer’s is due to a malfunctioning cytoskeleton and that destroying tau proteins can lead to cell death. Feinstein hypothesized the same action that destroys the cytoskeleton in cells treated with cancer drugs could be the same action that was triggered in the neuronal cells.

Prolonged stress does ugly things and now, possibly lead to Alzheimer’s disease (AD). Researchers at the Munich-based University of Minho in Braga, Portugal, have shown that stress, and the hormones released during stress, can accelerate the development of Alzheimer disease-like biochemical and behavioral pathology. Protein deposits in nerve cells are a typical feature of Alzheimer’s disease: the excessive alteration of the tau protein through the addition of phosphate groups — a process known as hyperphosphorylation — causes the protein in the cells to aggregate into clumps. Nerve cells die as a result and those in the hippocampus and the prefrontal cortex are important for learning, memory, and higher cognitive functions.

In this study, rats subjected to stress such as overcrowding and placement on a vibrating platform for one hour daily for one month showed increased hyperphosphorylation of tau protein in the hippocampus and prefrontal cortex. The animals that showed these changes in tau had deficient memories showing problems in the hippocampus area and impaired behavioral flexibility showing deficiency in the prefrontal cortex.

Less than 10 percent of Alzheimer cases are genetic. Previous studies have shown that stress leads to the formation of beta-amyloid, another protein implicated in Alzheimer’s disease. According to Osborne Almeida from the Max Planck Institute of Psychiatry, their findings indicate that stress hormones and stress can cause changes in the tau protein like those that arise in Alzheimer’s disease. The next step will be to see if results obtained in animals are applicable to the development of non-familial forms of Alzheimer’s disease.

Related Article: Stress Significantly Hastens Progression of Alzheimer’s Disease

Enhanced by Zemanta