Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCI researchers identify trigger for onset of Alzheimer’s, aiding search for new therapies

03.03.2005


Clearance of beta amyloid accumulation within neurons stops memory decline in mice



Researchers at UC Irvine have identified a trigger at the molecular level that marks the onset of memory decline in mice genetically engineered to develop brain lesions – in the form of plaques and tangles – associated with Alzheimer’s disease. The trigger is a protein called "beta amyloid" that accumulates within neurons in the mice’s brains. Although several researchers have studied the association between beta amyloid and memory, the UCI research team is the first to identify that early beta amyloid accumulation within neurons is the trigger for the onset of memory decline in Alzheimer’s.

"This finding has important and useful implications for the pharmaceutical industry in terms of developing drugs that can target beta amyloid as soon as it accumulates within the neurons," said Frank LaFerla, principal investigator of the research project, associate professor of neurobiology and behavior, and co-director of the UCI Institute for Brain Aging and Dementia. "Once the plaques and tangles form, it is too late."


The researchers report their findings in the March 3 issue of Neuron.

Although the production of beta amyloid occurs in all brains, healthy brains are able to clear away excess amounts. Brains with Alzheimer’s disease, on the other hand, are unable to control beta amyloid accumulation. In monitoring the mice from birth until six months, the researchers found that the mice had no Alzheimer’s disease symptoms at two months of age. At four months, however, the mice showed a decline in their long-term memory retention that the researchers found occurred in combination with the buildup of beta amyloid in neurons of the hippocampus, amygdala and cerebral cortex regions of the mice’s brains.

While the hippocampus is thought to play a key role in learning and memory formation, the amygdala is involved in computing the emotional significance of events. The cerebral cortex – the outer portion of the brain – is where thought processes occur. "It’s significant that the plaques and tangles did not show up in our mice at the four-month stage," said Lauren M. Billings, a postdoctoral researcher in the UCI School of Biological Sciences’ Department of Neurobiology and Behavior, and the first author of the study. "It suggests strongly that these hallmarks of Alzheimer’s disease contribute to cognitive decline only later and that the intraneuronal beta amyloid is the molecular trigger for the onset of this insidious disease."

Billings explained the mice were making more beta amyloid than their brains could clear naturally. When the researchers cleared away the beta amyloid within the neurons, however, they were able to correct the memory impairments in the mice. Moreover, the researchers found that a reemergence of beta amyloid inside the neurons in the mice marked again the onset of memory problems.

In their study, the researchers used mice that were genetically engineered to develop Alzheimer’s disease, a necessary step in the research since mice ordinarily do not develop symptoms of the disease. The molecular and cellular changes that trigger the onset of memory decline in the human brain with Alzheimer’s disease are currently unknown and constitute a difficult problem to address. Hence, researchers turn to animal models, such as mice.

The UCI researchers studied 270 mice from birth until six months. They placed the mice in a water maze set in a water tank where the mice were encouraged repeatedly to locate a hidden platform in the tank by making spatial associations in the room to facilitate their search. After the platform was removed, the researchers monitored in subsequent trials how fast the mice swam to where the platform used to be – an indication of how well the mice remembered the platform’s location. At four months of age, the mice developed memory problems together with beta amyloid accumulation in their brain’s neurons.

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly in the United States, affecting 4.5-5 million adults – 10 times more than those affected by Parkinson’s disease. Starting with mild memory problems and ending with severe brain damage, Alzheimer’s usually begins after the age of 60, the risk increasing with age. If no effective therapies are developed, by 2050 it is estimated that 13 million Americans will have the disease. In the United States, five percent of the population over age 65 and one-third of the population over age 85 are afflicted by it. It is the third most expensive disease to treat and is the third leading cause of death, trailing cancer and coronary heart disease.

Iqbal Pittalwala | EurekAlert!
Further information:
http://www.uci.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>