Chronic stress spawns protein aggregates linked to Alzheimer's

March 26, 2012, University of California - San Diego
Exposing mice to 14 days of repeated stress resulted in an accumulation of insoluble phosphorylated tau protein aggregates in brain cells, visualized in this electron micrograph. Credit: Image courtesy of Robert Rissman, UC San Diego

Repeated stress triggers the production and accumulation of insoluble tau protein aggregates inside the brain cells of mice, say researchers at the University of California, San Diego School of Medicine in a new study published in the March 26 Online Early Edition of the Proceedings of the National Academy of Sciences.

The aggregates are similar to neurofibrillary tangles or NFTs, modified protein structures that are one of the physiological hallmarks of Alzheimer's disease. Lead author Robert A. Rissman, PhD, assistant professor of neurosciences, said the findings may at least partly explain why clinical studies have found a strong link between people prone to stress and development of sporadic Alzheimer's disease (AD), which accounts for up to 95 percent of all AD cases in humans.

"In the mouse models, we found that repeated episodes of , which has been demonstrated to be comparable to what humans might experience in ordinary life, resulted in the phosphorylation and altered solubility of tau proteins in neurons," Rissman said. "These events are critical in the development of NFT pathology in Alzheimer's disease."

The effect was most notable in the hippocampus, said Rissman, a region of the brain linked to the formation, organization and storage of memories. In AD patients, the hippocampus is typically the first region of the brain affected by tau pathology and the hardest-hit, with substantial cell death and shrinkage.

Not all forms of stress are equally threatening. In earlier research, Rissman and colleagues reported that – a single, passing episode – does not result in lasting, debilitating long lasting changes in accumulation of phosphorylated tau. Acute stress-induced modifications in the cell are transient, he said, and on the whole, probably beneficial.

"Acute stress may be useful for brain plasticity and helping to facilitate learning. Chronic stress and continuous activation of stress pathways may lead to pathological changes in stress circuitry. It may be too much of a good thing." As people age, perhaps their neuronal circuits do too, he said, becoming less robust and perhaps less capable of completely rebounding from the effects of stress.

"Age is the primary, known risk factor for Alzheimer's disease. It may be that as we age, our neurons just aren't as plastic as they once were and some succumb."

The researchers observed that stress cues impacted two key corticotropin-releasing factor receptors, suggesting a target for potential therapies. Rissman noted drugs already exist and are in human trials (for other conditions) that modulate the activity of these receptors.

"You can't eliminate stress. We all need to be able to respond at some level to stressful stimuli. The idea is to use an antagonist molecule to reduce the effects of stress upon neurons. The stress system can still respond, but the response in the brain and hippocampus would be toned down so that it doesn't result in harmful, permanent damage."

Explore further: Stress may increase risk for Alzheimer's disease

Related Stories

Stress may increase risk for Alzheimer's disease

May 26, 2011
Stress promotes neuropathological changes that are also seen in Alzheimer's disease. Scientists from the Max Planck Institute of Psychiatry in Munich have discovered that the increased release of stress hormones in rats leads ...

Mechanism sheds light on how the brain adapts to stress

January 25, 2012
Scientists now have a better understanding of the way that stress impacts the brain. New research, published by Cell Press in the January 26 issue of the journal Neuron, reveals pioneering evidence for a new mechanism of ...

Scientists uncover mechanism by which chronic stress causes brain disease

June 29, 2011
Chronic stress has long been linked with neurodegeneration. Scientists at USC now think they may know why.

Recommended for you

Alzheimer's disease: Neuronal loss very limited

January 17, 2018
Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. A joint ...

Anxiety: An early indicator of Alzheimer's disease?

January 12, 2018
A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of ...

One of the most promising drugs for Alzheimer's disease fails in clinical trials

January 11, 2018
To the roughly 400 clinical trials that have tested some experimental treatment for Alzheimer's disease and come up short, we can now add three more.

Different disease types associated with distinct amyloid-beta prion strains found in Alzheimer's patients

January 9, 2018
An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. In their paper published in Proceedings of the National ...

Advances in brain imaging settle debate over spread of key protein in Alzheimer's

January 5, 2018
Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer's disease - and hence that blocking its spread ...

Molecular mechanism behind HIV-associated dementia revealed

January 5, 2018
For the first time, scientists have identified and inhibited a molecular process that can lead to neurodegeneration in patients with HIV, according to a Northwestern Medicine study published in Nature Communications.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.