(Press-News.org) SAN FRANCISCO, CA – November 3, 2010—Scientists at the Gladstone Institute of Neurological Disease (GIND) have offered new information about the events that underlie the "spread" of Alzheimer's disease (AD) throughout the brain. The research, published in the November 4th issue of the journal Neuron, follows disease progression from a vulnerable brain region that is affected early in the disease to interconnected brain regions that are affected in later stages. The findings may contribute to design of therapeutic interventions, as targeting the brain region where AD originates might be simpler than targeting multiple brain areas.
An alteration in brain levels of amyloid β proteins (Aβ) plays a major role in AD, a devastating neurodegenerative disorder that causes progressive cognitive impairment and memory loss. AD is characterized by abnormal accumulation of Aβ in the brain, which leads to the formation of protein aggregates that are toxic to neurons. Aβ peptides are generated when a large protein called amyloid precursor protein (APP) is cut up into smaller pieces.
One of the first brain regions affected in AD is the entorhinal cortex (EC). Connections between the EC and another brain region called hippocampus are critical for memory, and disruption of this circuit may play a role in memory impairment in the beginning stages of AD.
"It is not clear how EC dysfunction contributes to cognitive decline in AD or whether early vulnerability of the EC initiates the spread of dysfunction through interconnected neural networks," explained senior study author and GIND director Lennart Mucke , MD. "To address these questions, we studied transgenic mice with mutant APP expressed primarily in neurons of the EC."
The majority of current mouse models of AD express mutant proteins throughout the brain, making it difficult to identify the role of any specific brain region in AD-related dysfunction.
Dr. Mucke and colleagues found that expressing mutant APP and Aβ selectively in the EC led to age-dependent deficits in learning and memory, and other behavioral deficits including hyperactivity and disinhibition. Importantly, these abnormalities are similar to those observed in mouse models of AD with mutant APP expression throughout the brain. The researchers also observed abnormalities in parts of the hippocampus that receive input from the EC, including dysfunction of synapses and Aβ deposits.
"Our findings directly support the hypothesis that AD-related dysfunction is propagated through networks of neurons, with the EC as an important hub region of early vulnerability," concluded Dr. Julie Harris, the lead author of the study. "Although additional studies are needed to better understand how events in the EC are related to AD, it is conceivable that early interference in the EC might be of therapeutic benefit, perhaps halting disease progression."
###
Also contributing to this study were Gladstone scientists Nino Devidze, Laure Verret, Kaitlyn Ho, Brian Halabisky, Myo T. Thwin, Daniel Kim, Patricia Hamto, Iris Lo, Gui-Qiu Yu, Jorge J. Palop, and Professor Eliezer Masliah of the University of California at San Diego.
The study was supported by grants from the National Institutes of Health and a fellowship from the McBean Foundation.
Lennart Mucke's primary affiliation is with the Gladstone Institute of Neurological Disease, where he is Director/Senior Investigator and where his laboratory is located and his research is conducted. He is also the Joseph B. Martin Distinguished Professor of Neuroscience at UCSF.
Gladstone Institutes is a nonprofit, independent research and educational institution, consisting of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology, and the Gladstone Institute of Neurological Disease. Independent in its governance, finances and research programs, Gladstone shares a close affiliation with UCSF through its faculty, who hold joint UCSF appointments.
END
Many gene variants have been linked to autism, but how do these subtle changes alter the brain, and ultimately, behavior?
Using a blend of brain imaging and genetic detective work, scientists at UCLA's David Geffen School of Medicine and Semel Institute for Neuroscience and Human Behavior are the first to illustrate how genetic variants rewire the brain. Published in the Nov. 3 online edition of Science Translational Medicine, their discovery offers the crucial missing physical evidence that links altered genes to modified brain function and learning.
"This is a key ...
CAMBRIDGE, Mass. -- Humans have long taken advantage of the huge variety of medicinal compounds produced by plants. Now MIT chemists have found a new way to expand plants' pharmaceutical repertoire by genetically engineering them to produce unnatural variants of their usual products.
The researchers, led by Associate Professor Sarah O'Connor, have added bacterial genes to the periwinkle plant, enabling it to attach halogens such as chlorine or bromine to a class of compounds called alkaloids that the plant normally produces. Many alkaloids have pharmaceutical properties, ...
Brain research over the past 30 years has shown that if a part of the brain controlling movement or sensation or language is lost because of a stroke or injury, other parts of the brain can take over the lost function – often as well as the region that was lost.
New research at the University of California, Berkeley, shows that this holds true for memory and attention as well, though – at least for memory – the intact brain helps out only when needed and conducts business as usual when it's not.
These results support the hypothesis that memory is not stored in one place, ...
Researchers at the University of Arizona (UA), Tucson, have developed a holographic system that can transmit a series of 3D images in near-real-time, a precursor to holographic videoconferencing.
The system incorporates a novel, photorefractive polymer--one that can rapidly refresh holographic images and is scalable for production--coupled to a unique system for recording and transmitting 3D images of individuals and objects via Ethernet.
Lead author Pierre-Alexandre Blanche and his colleagues from the university and Nitto Denko Technical Corp. of Oceanside, Calif., ...
Stroke is the leading cause of adult disability, due to the brain's limited capacity for recovery. Physical rehabilitation is the only current treatment following a stroke, and there are no medications available to help promote neurological recovery.
Now, a new UCLA study published in the Nov. 11 issue of the journal Nature offers insights into a major limitation in the brain's ability to recover function after a stroke and identifies a promising medical therapy to help overcome this limitation.
Researchers interested in how the brain repairs itself already know ...
Using the Canadian Light Source synchrotron and the Stanford Synchrotron Radiation Lightsource, a team of researchers from the University of British Columbia has shed light on the ryanodine receptor, a structure within muscle cells that has been linked to life-threatening congenital heart conditions.
The findings were published online today in the journal Nature.
"The ryanodine receptor is a complex molecular machine within muscle cells," says Filip Van Petegem, an assistant professor in UBC's Department of Biochemistry and Molecular Biology and lead author of the study. ...
TORONTO, Ont. — November 1, 2010 — A drug commonly used in Japan and Korea to treat asthma has been found to stop the spread of breast cancer cells traditionally resistant to chemotherapy, according to a new study led by St. Michael's pathologist Dr. Gerald Prud'homme.
"Tranilast, a drug approved for use in Japan and South Korea, and not in use in Canada or the U.S., has been used for more than two decades to treat asthma and other allergic disorders including allergic rhinitis and atopic dermatitis," Dr. Prud'homme says. "Now, our study is the first to discover it not ...
VIDEO:
Niemann-Pick type C, a fatal genetic disorder that frequently takes years to diagnose, may now be detectable with a simple blood test, according to researchers at Washington University School of...
Click here for more information.
A fatal genetic disorder that frequently takes years to diagnose may soon be detectable with a simple blood test, researchers at Washington University School of Medicine in St. Louis and the National Institutes of Health (NIH) report this week ...
TEMPE, Ariz. – Volunteering is known to provide health benefits to the person doing the volunteering. Now, a new study finds that older adults with functional limitations (trouble conducting daily tasks like cooking meals) in particular appear to reap the benefits from helping others.
The new study addresses the question of whether the impact of volunteering on risk of mortality was stronger for older adults with or without functional limitations.
"As functional limitations increase, the risk of dying increases, but not among those who volunteered," said Morris Okun, ...
A gamma-ray burst is an immensely powerful blast of high-energy light thought to be generated by a collapsing star in a distant galaxy, but what this collapse leaves behind has been a matter of debate.
A new analysis of four extremely bright bursts observed by NASA's Fermi satellite suggests that the remnant from a long-duration gamma-ray burst is most likely a black hole – not a rapidly spinning, highly magnetized neutron star, or magnetar since such a burst emits more energy than is theoretically possible from a magnetar.
"Some of the events we have been finding ...
