Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

New, improved mouse model of human Alzheimer's may enable drug discovery

09.11.2012
Researchers at the University of Illinois at Chicago College of Medicine have developed a transgenic mouse that carries a human gene known to increase risk of Alzheimer's 15-fold.

This new mouse mimics the genetics of the human disease more closely than any of the dozen existing mouse models and may prove more useful in the development of candidate drugs to prevent or treat the disease.

The new mouse model provides new evidence for the earliest cause of Alzheimer's, researchers report in a study to be published in the December issue of the Journal of Biological Chemistry and now available online.

The model is a cross between an existing transgenic Alzheimer's mouse and a mouse carrying fully human apoE, a gene that in one of its three variants, apoE4, is the greatest genetic risk factor for Alzheimer's in the human population.

UIC biochemist Mary Jo LaDu says amyloid-beta, a peptide, or small protein, is known to underlie the disease and is a key component of the plaques observed in the brains of deceased Alzheimer's patients at autopsy. But in addition to clumping to form those large, visible plaques, the sticky molecule is also found in smaller, soluble aggregates called oligomers -- which may be the actual culprit.

"Though for a long time it was thought that amyloid plaques might cause the nerve death seen in Alzheimer's, researchers now believe that the neurotoxicity may lie in the smaller, soluble, oligomeric forms," said LaDu, who is associate professor of anatomy and cell biology at the UIC College of Medicine and principal investigator of the study.

But the researchers still faced a hurdle before they could test their hypothesis about the role of oligomeric amyloid-beta, said one of her UIC coworkers.

"There are few methods for detecting the different aggregate forms of amyloid-beta," said Leon Tai, a research assistant professor working with LaDu. So, he said, the team developed a highly specific monoclonal antibody, which enabled them to assay only the specific oligomeric form of amyloid-beta.

This new monoclonal antibody, along with the new mouse model, "allowed us to identify the earliest accumulations of amyloid-beta and the differences related to the different forms of apoE," said LaDu.

The results were definitive: transgenic mice with apoE4 show an increase in the oligomeric form of amyloid-beta compared to mice carrying the other, more benign versions of apoE, providing a mechanism for apoE-induced Alzheimer's risk. Thus, previous transgenic mice lacking this interaction were poor models, say the researchers.

In addition, if oligomeric amyloid-beta is the cause of the disease, then it is also the earliest disease marker. Thus, the new model offers a clear picture of therapeutic effects on the cause of the disease not possible with the methods and models currently available.

"More than just an Alzheimer's risk factor, patients with apoE4 often respond differently to therapeutics in clinical trials, in many cases negatively," said Tai, whose background includes drug discovery. "However, preclinical compound testing in transgenic mouse models that express human apoE has not been possible until now."

"A pre-clinical model for testing these compounds has been badly needed, so we don't find ourselves in clinical trials with therapeutics that fail," said LaDu. She has begun collaborations with other researchers at UIC and worldwide to focus on drug discovery.

"We are actively working to test and develop novel compounds that we believe will benefit all Alzheimer's patients," she said.

The research was funded by an Alzheimer's Association Zenith Grant, a UIC Center for Clinical and Translational Science Pilot Award, and National Institutes of Health/National Institute of Aging Program Project Grant NIH/NIA PO1AG030128.

Katherine Youmans, former UIC graduate student and now a postdoctoral researcher at Boston University, is first author of the paper. In addition to Youmans, Tai and LaDu, other authors are Evelyn Nwabuisi-Heath, Lisa Jungbauer and Chunjiang Yu from UIC; Takahisa Kanekiyo, Ming Gan and Guojun Bu of the Mayo Clinic in Jacksonville, Fla.; Jungsu Kim of Washington University School of Medicine; William Eimer of the Northwestern University Feinberg School of Medicine; G. William Rebeck of Georgetown University and Edwin Weeber of the University of South Florida.

Editor's Note: Images available at http://newsphoto.lib.uic.edu/v/LaDu/

Jeanne Galatzer-Levy | EurekAlert!
Further information:
http://www.uic.edu

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Klima-Satellit: Mit robuster Lasertechnik Methan auf der Spur

Hitzewellen in der Arktis, längere Vegetationsperioden in Europa, schwere Überschwemmungen in Westafrika – mit Hilfe des deutsch-französischen Satelliten MERLIN wollen Wissenschaftler ab 2021 die Emissionen des Treibhausgases Methan auf der Erde erforschen. Möglich macht das ein neues robustes Lasersystem des Fraunhofer-Instituts für Lasertechnologie ILT in Aachen, das eine bisher unerreichte Messgenauigkeit erzielt.

Methan entsteht unter anderem bei Fäulnisprozessen. Es ist 25-mal wirksamer als das klimaschädliche Kohlendioxid, kommt in der Erdatmosphäre aber lange nicht...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: Die Schweiz in Pole-Position in der neuen ESA-Mission

Die Europäische Weltraumagentur ESA gab heute grünes Licht für die industrielle Produktion von PLATO, der grössten europäischen wissenschaftlichen Mission zu Exoplaneten. Partner dieser Mission sind die Universitäten Bern und Genf.

Die Europäische Weltraumagentur ESA lanciert heute PLATO (PLAnetary Transits and Oscillation of stars), die grösste europäische wissenschaftliche Mission zur...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

Von Batterieforschung bis Optoelektronik

23.06.2017 | Veranstaltungen

10. HDT-Tagung: Elektrische Antriebstechnologie für Hybrid- und Elektrofahrzeuge

22.06.2017 | Veranstaltungen

„Fit für die Industrie 4.0“ – Tagung von Hochschule Darmstadt und Schader-Stiftung am 27. Juni

22.06.2017 | Veranstaltungen

 
VideoLinks
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Radioaktive Elemente in Cassiopeia A liefern Hinweise auf Neutrinos als Ursache der Supernova-Explosion

23.06.2017 | Physik Astronomie

Dünenökosysteme modellieren

23.06.2017 | Ökologie Umwelt- Naturschutz

Makro-Mikrowelle macht Leichtbau für Luft- und Raumfahrt effizienter

23.06.2017 | Materialwissenschaften