Brain cell activity regulates Alzheimer's protein

February 26, 2014

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

Lifestyle changes to stave off Alzheimer's? Hints, no proof

July 20, 2017
There are no proven ways to stave off Alzheimer's, but a new report raises the prospect that avoiding nine key risks starting in childhood just might delay or even prevent about a third of dementia cases around the world.

Blood test identifies key Alzheimer's marker

July 19, 2017
A new study led by researchers at Washington University School of Medicine in St. Louis suggests that measures of amyloid beta in the blood have the potential to help identify people with altered levels of amyloid in their ...

Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

July 19, 2017
The old real estate adage about "location, location, location" might also apply to the biochemical genesis of Alzheimer's disease, according to new research from the University of British Columbia.

Brain scans may change care for some people with memory loss

July 19, 2017
Does it really take an expensive brain scan to diagnose Alzheimer's? Not everybody needs one but new research suggests that for a surprising number of patients whose memory problems are hard to pin down, PET scans may lead ...

Can poor sleep boost odds for Alzheimer's?

July 18, 2017
(HealthDay)— Breathing problems during sleep may signal an increased risk for Alzheimer's disease, a trio of studies suggests.

Hearing is believing: Speech may be a clue to mental decline

July 17, 2017
Your speech may, um, help reveal if you're uh ... developing thinking problems. More pauses, filler words and other verbal changes might be an early sign of mental decline, which can lead to Alzheimer's disease, a study suggests.

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.