Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Different forms of amyloid beta in Alzheimer’s disease harm neurons in different ways

01.06.2006


Study suggests retargeting efforts to slow or stop neural cell loss in the neurodegenerative disorder



Researchers at UC Irvine have shown that different forms of amyloid beta lead to neural damage in different ways, leading to an increasingly complex view of amyloid toxicity in the Alzheimer brain. The finding could modify the way therapeutic approaches for the treatment of Alzheimer’s disease are designed.

The researchers studied the effects of different forms of the amyloid beta peptide on human brain cells. Amyloid beta accumulation is one of two hallmarks of Alzheimer’s disease and is considered a major target for researchers looking into therapies for the treatment of the disease. After death, most amyloid beta found in the brains of Alzheimer’s patients is in fibrillar form – long, insoluble fibers bound together in deposits called senile plaques; however, there are also soluble forms of amyloid beta, or oligomers, that may decisively contribute to neural degeneration.


The experiments conducted at UCI showed that the soluble forms of amyloid beta are much more toxic and lead to neuronal death in as little as 12 hours. The fibrillar form, meanwhile, does not actually kill the neurons, but slowly, over a period of 10 or more days, renders them useless.

Not known is whether the soluble amyloid beta in the Alzheimer brain eventually turns into the fibrillar kind, or whether the two are completely different.

The findings were published this week in the Journal of Neuroscience.

“These findings are quite significant because, although both fibrils and oligomers may contribute to dementia, they do so in very different ways over different time spans,” said Jorge Busciglio, an assistant professor of neurobiology and behavior. “This complexity of the amyloid beta species will require more sophisticated therapeutic approaches. For example, it might be dangerous to create compounds that target fibrillar amyloid and try to break them up, because if the fibers dissolve into the soluble form, that could actually speed up cell death and the onset of dementia rather than treat it.”

Atul Deshpande, a graduate student in Busciglio’s laboratory, tested one preparation of fibrillar amyloid beta and two soluble ones, which resemble the types found in the brains of Alzheimer’s patients. In less than 12 hours, the human neurons exposed to one of the two soluble forms started to die. Most of the cells were dead after 24 hours. The cells exposed to the other soluble form took about five times longer to die. In contrast, the brain cells treated with the fibrillar form slowly degenerated. The axons and dendrites in the cells became twisted and rendered the cell functionally useless. For the most part, however, the cells did not die.

According to the scientists, previous research has shown that the brain levels of soluble amyloid beta appear to correlate better with severity of cognitive impairment than the number and density of plaques found in the brain. Then, the more soluble beta amyloid is present, the more severe and rapid the onset of the disease.

Researchers now will have to determine why the soluble form of beta amyloid is so much more toxic. One theory is it binds to neuronal connections, or gateways into the cell, and gives soluble amyloid beta easier, quicker access into the neuron. The UCI research also showed that the soluble form quickly impairs the function of mitochondria, the cells’ energy generators. Brain cells consume more energy than any other cell in the body. If that energy source dies, the cells die as well.

Alzheimer’s disease is a progressive neurodegenerative disorder, affecting 4.5 million to 5 million adults in the United States. If no effective therapies are developed, it is estimated that 13 million Americans will be afflicted with the disease by 2050. It is the third-most-expensive disease to treat and the third-leading cause of death, behind cancer and coronary heart disease.

Along with Busciglio and Deshpande, researchers on the study were Charles Glabe, a professor of molecular biology and biochemistry, and graduate researcher Erene Mina. The study was funded by grants from the Alzheimer’s Association, the National Institutes of Health and the Larry L. Hillblom Foundation.

About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.3 billion. For more UCI news, visit www.today.uci.edu.

Television: UCI has a broadcast studio available for live or taped interviews. For more information, visit www.today.uci.edu/broadcast.

News Radio: UCI maintains on campus an ISDN line for conducting interviews with its faculty and experts. The use of this line is available free-of-charge to radio news programs/stations who wish to interview UCI faculty and experts. Use of the ISDN line is subject to availability and approval by the university.

Farnaz Khadem | EurekAlert!
Further information:
http://www.uci.edu

More articles from Physics and Astronomy:

nachricht SF State astronomer searches for signs of life on Wolf 1061 exoplanet
20.01.2017 | San Francisco State University

nachricht Molecule flash mob
19.01.2017 | Technische Universität Wien

All articles from Physics and Astronomy >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>