Neural activity accelerates its spread through the brain
A toxic Alzheimer's protein can spread through the brain--jumping from one neuron to another--via the extracellular space that surrounds the brain's neurons, suggests new research from Columbia University Medical Center.
The study has been published online in Nature Neuroscience.
The spread of the protein, called tau, may explain why only one area of the brain is affected in the early stages of Alzheimer's but multiple areas are affected in later stages of the disease.
"By learning how tau spreads, we may be able to stop it from jumping from neuron to neuron," said Karen Duff, PhD, professor in the department of pathology and cell biology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) and professor of psychiatry (at New York State Psychiatric Institute.) "This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia."
The idea the Alzheimer's can spread through the brain first gained support a few years ago when Duff and other Columbia researchers discovered that tau spread from neuron to neuron through the brains of mice.
In the new study, lead scientist Jessica Wu, PhD, a former post-doctoral researcher at the Taub Institute who is currently at Massachusetts Institute of Technology, discovered how tau travels by tracking the movement of tau from one neuron to another. Tau, she found, can be released by neurons into extracellular space, where it can be picked up by other neurons. Because tau can travel long distances within the neuron before its release, it can seed other regions of the brain.
"This finding has important clinical implications," explained Dr. Duff. "When tau is released into the extracellular space, it would be much easer to target the protein with therapeutic agents, such as antibodies, than if it had remained in the neuron."
A second interesting feature of the study is the observation that the spread of tau accelerates when the neurons are more active. Two team members, Abid Hussaini, PhD, and Gustavo Rodriguez, PhD, showed that stimulating the activity of neurons accelerated the spread of tau through the brain of mice and led to more neurodegeneration.
Although more work is needed to examine whether those findings are relevant for people, "they suggest that clinical trials testing treatments that increase brain activity, such as deep brain stimulation, should be monitored carefully in people with neurodegenerative diseases," said Dr. Duff.
The study is titled, "Neuronal activity enhances tau propagation and tau pathology in vivo."
Authors included Jessica W. Wu, S. Abid Hussaini, Isle Bastille, Gustavo A. Rodriguez, Kelly Rilett, Hongjun Fu, Rick A. C. M. Boonen, Mathieu Hreman, Eden Nahmani, Sheina Emrani, Y Helen Figueroa, Catherine L. Clelland, and Karen E. Duff (Taub Institute, Columbia University Medical Center, New York, NY), Ana Mrejeru (Department of Neurology, Columbia University Medical Center, New York, NY), David W. Sanders and Marc I. Diamond (Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX), Casey Cook (Department of Neuroscience, Mayo Clinic, Jacksonville, FL), and Selina Wray (Institute of Neurology, University College, London, UK).
This work was supported by a BrightFocus Foundation fellowship, NIH/NINDS grants NS081555 and NS074874, Cure Alzheimer's Fund, the Parkinson's Disease Foundation, NIH/NIA grants AG050425 and AA19801, and the NIHR Queen Square Dementia Biomedical Research Unit.
The authors declare no competing financial interests.
Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.
Karin Eskenazi | EurekAlert!
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy