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 Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>