Brain cell activity regulates Alzheimer's protein

February 26, 2014, Washington University School of Medicine

Increased brain cell activity boosts brain fluid levels of a protein linked to Alzheimer's disease, according to new research from scientists at Washington University School of Medicine in St. Louis.

Tau protein is the main component of neurofibrillary tangles, one of the hallmarks of Alzheimer's disease. It has been linked to other neurodegenerative disorders, including frontotemporal dementia, supranuclear palsy and corticobasal degeneration.

"Healthy brain cells normally release into the cerebrospinal fluid and the interstitial fluid that surrounds them, but this is the first time we've linked that release in living animals to brain cell activity," said senior author David M. Holtzman, MD. "Understanding this link should help advance our efforts to treat Alzheimer's and other neurodegenerative disorders associated with the .

The study appears online in the Journal of Experimental Medicine.

Tau protein stabilizes microtubules, which are long columns that transport supplies from the center of the cell to the distant ends of the cell's branches. Some tau in the cell is not bound to microtubules. This tau can become altered and clump together inside brain cells, forming structures called tangles. Scientists have tracked the spread of these clumps through brain networks in animal models.

"In Alzheimer's disease, you first see clumps of tau in a region called the entorhinal cortex, and then in the hippocampus, and it continues to spread through the brain in a regular pattern," said Holtzman, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "In another disorder, supranuclear palsy, tau clumps first appear in the brain stem and then spread to regions that the brain stem projects to."

These regular patterns of tau spread through brain networks have led scientists to speculate that dysfunctional tau travels to different brain regions via synapses—the areas where individual nerve cells communicate with each other.

Holtzman's results support this hypothesis, showing that when nerve cells "talk" to each other, tau levels go up in the fluids between those cells, suggesting that brain cells are secreting tau when they send signals.

So far, the researchers only have been able to measure single copies of tau in brain fluid, not the tau clumps. They are looking for a way to detect the clumps. If brain cells can secrete and take in clumps of tau, the scientists believe, these may cause previously normal tau in the receiving cell to become corrupted, fostering the spread of a form of tau involved in disease.

"We also want to know whether brain cells are secreting tau as waste or if tau has a function to perform outside the cell," Holtzman said. "For example, there have been hints that tau may modulate how easy or difficult it is to get to communicate with each other."

Explore further: Alzheimer's protein detected in brain fluid of healthy mice

More information: The Journal of Experimental Medicine, published online Feb. 18, 2014. DOI: 10.1084/jem.20131685

Related Stories

Alzheimer's protein detected in brain fluid of healthy mice

September 21, 2011
(Medical Xpress) -- One of the most promising markers of Alzheimer’s disease, previously thought only to be inside nerve cells, now appears to be normally released from nerve cells throughout life, according to researchers ...

Newly identified antibodies effectively treat Alzheimer's-like disease in mice

September 26, 2013
Alzheimer's disease is characterized by the accumulation of particular toxic proteins in the brain that are believed to underlie the cognitive decline in patients. A new study conducted in mice suggests that newly identified ...

Receptor may aid spread of Alzheimer's and Parkinson's in brain

August 23, 2013
(Medical Xpress)—Scientists at Washington University School of Medicine in St. Louis have found a way that corrupted, disease-causing proteins spread in the brain, potentially contributing to Alzheimer's disease, Parkinson's ...

Transmission of tangles in Alzheimer's mice provides more authentic model of tau pathology

January 15, 2013
Brain diseases associated with the misformed protein tau, including Alzheimer's disease and frontotemporal lobar degeneration with tau pathologies, are characterized by neurofibrillary tangles (NFTs) comprised of pathological ...

Neuronal activity induces tau release from healthy neurons

February 15, 2013
Researchers from King's College London have discovered that neuronal activity can stimulate tau release from healthy neurons in the absence of cell death. The results published by Diane Hanger and her colleagues in EMBO reports ...

From trauma to tau: Researchers tie brain injury to toxic form of protein

May 29, 2013
University of Texas Medical Branch at Galveston researchers have uncovered what may be a key molecular mechanism behind the lasting damage done by traumatic brain injury.

Recommended for you

Rocky start for Alzheimer's drug research in 2018

January 19, 2018
The year 2018, barely underway, has already dealt a series of disheartening blows to the quest for an Alzheimer's cure.

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 ...

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.