Research Suggests Chronic Stress Linked to Alzheimer's Disease

The tau protein aggregates observed during the study conducted on brain cells of mice were similar to the tau proteins that are also found in Alzheimer's disease in humans. The results have been published in the online edition of the Proceedings of the National Academy of Sciences.

Stress is a natural response to difficult situations and in the recent years it has also been linked to psychiatric conditions such as anxiety and depression. On an upbeat note, not all kinds of stress are harmful. 'Acute stress', which is event-free and may even prove to be beneficial, is believed to help improve brain plasticity and develop learning.

However the word 'stress' frequently indicates chronic stress, an affected state of mind that has now integrated in our daily life. Work place troubles, relationship problems, financial, health or other emotional challenges contribute to chronic stress.

Chronic stress is 'harmful' as it brings about pathological changes in the body and is known to have severe health implications. The findings from the present study confirm those made by earlier clinical findings, which suggest that individuals prone to stress are more likely to develop sporadic Alzheimer's disease (AD), which, incidentally, accounts for more than 90% of people with AD.

When people begin to age their neurons become less capable of handling the effects of stress. During stressful situations the hypothalamus of the brain releases the Corticotropin Releasing Hormone (CRH). The role of the CRH is to stimulate the pituitary gland to release the adrenocorticotropic hormone which would act on the adrenal glands to release the stress hormone, cortisol.

The pathology of the AD reveals the involvement of two different proteins, beta-amyloid plaques and neurofibrillary tangles (NFTs). The NFTs comprise of aggregates of a protein called Tau. The role of tau protein is to maintain cellular structure and in the building of the cytoskeleton.

In a person with Alzheimer, the end of the tau protein gets phosphorylated, as a result of which they form aggregates. When the aggregates amplify they form neurofibrillary tangles that correlate with a person's cognitive decline, a symptom of Alzheimer's disease. Research on tau proteins could throw light on the symptoms and progress of AD, which, in turn, would help in the management of the condition.

During experiments conducted on mouse models, repeated episodes of human-like stress resulted in the phosphorylation and altered the solubility of neuronal tau proteins. This process is most evident in the hippocampus, which is the seat of memory and, also the area that is first and hardest hit during the unfolding of AD pathology.

In the above-said experiments, two corticotrophin - releasing factor receptors were particularly impacted by stress. Antagonists against these receptors reduced stress- effects. Drugs are being tried that modulate the functioning of these receptors.

The critical research however has raised many doubts. First of all, there is no clear-cut evidence to suggest that NFTs cause AD. Secondly, no cognitive decline was noticed in mice despite the increase in phosphorylated tau. Thirdly, the possibility that the mice might have got used to the repeated stress cannot be ruled out and therefore, using a different kind of stress after a certain period might have been more effective.

Despite the loopholes, this interesting work carried out by Rissman et al has immense potential but needs added evidence for larger and sustained effect.

Reference:

Robert A. Rissmann, Michael A. Staup, Allyson Roe Lee, Nicholas J. Justice, Kenner C. Rice, Wylie Vale, and Paul E. Sawchenko (2012):" Corticotropin-releasing factor receptor-dependent effects of repeated stress on tau phosphorylation, solubility, and aggregation": PNAS, 2012.

Source-Medindia