Last year, this same group of researchers found that they could completely prevent Alzheimer’s disease in mice genetically engineered with a human Alzheimer’s gene—“Mouzheimer’s”—by blocking a single site of cleavage of one molecule, called APP for amyloid precursor protein. Normally, this site on APP is attacked by molecular scissors called caspases, but blocking that process prevented the disease.
Now they have studied human brain tissue and found that, just as expected, patients suffering from AD clearly show more of this cleavage process than people of the same age who do not have the disease. However, when they extended their studies to much younger people without Alzheimer’s disease, they were astonished to find an apparent paradox: these younger people displayed as much as ten times the amount of the same cleavage event as the AD patients. The researchers now believe they know why.
The Buck Institute study implicates a biochemical “switch” associated with that cleavage of APP, causing AD brains to become stuck in the process of breaking memories, and points to AD as a syndrome affecting the plasticity or malleability of the brain. The study, due to be published in the March 7 issue of the Journal of Alzheimer’s Disease, provides new insight into a molecular event resulting in decreased brain plasticity, a central feature of AD.
“Young brains operate like Ferraris – shifting between forward and reverse, making and breaking memories with a facility that surpasses that of older brains, which are less plastic,” said Dale Bredesen, MD, Buck Institute faculty member and leader of the research group. “We believe that in aging brains, AD occurs when the ‘molecular shifting switch’ gets stuck in the reverse position, throwing the balance of making and breaking memories seriously off kilter.”
In previous research, lead author Veronica Galvan, PhD, prevented this cleavage in mice genetically engineered to develop the amyloid plaques and deposits associated with AD. These surprising mice had normal memories and showed no signs of brain shrinkage or nerve cell damage, despite the fact that their brains were loaded with the sticky A-beta plaques that are otherwise associated with Alzheimer’s disease.
“A-beta is produced throughout the brain throughout life; we believe that it is a normal regulator of the synapses, the connections between neurons,” said Galvan, who added that AD, like cancer, is a disease in which imbalanced cell signaling plays an important role.
“The fact that many people develop A-beta plaques yet show no symptoms of AD tells us that the downstream signaling of A-beta—not just A-beta itself—is critical,” said Bredesen, “and these pathways can be targeted therapeutically. Simply put, we can restore the balance.” Continuing research at the Buck Institute focuses on nerve signaling and efforts to “disconnect” the molecular mechanism that throws memory-making in the reverse direction, as well as understanding mechanisms that support brain cell connections that are crucial to the process of memory making.
AD is an incurable neurodegenerative disease currently affecting 5.1 million Americans. AD results in dementia and memory loss, seriously affecting a person’s ability to carry out activities of daily living. AD costs the U.S. $148 billion annually, in addition to untold family suffering.
Joining Bredesen and Galvan as co-authors of the paper, “C-terminal cleavage of the amyloid precursor protein at Asp664: a switch associated with Alzheimer’s disease” are Surita Banwait, BA; Junli Zhang, MD; Olivia F. Gorostiza, Marina Ataie, BS; Wei Huang, BS; and Danielle Crippen, BA of the Buck Institute, as well as Edward H. Koo, MD, of the University of California, San Diego, Department of Neuroscience. The work was supported by the Joseph Drown Foundation, The National Institute on Aging, the Bechtel Foundation, and the Alzheimer’s Association.
Kris Rebillot | alfa
Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine
NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences