Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A few more pieces for the puzzle that is Alzheimer’s disease

11.01.2008
GPEARI / MCTES - Gabinete de Planeamento, Estratégia, Avaliação e Relações Internacionais / Ministério da Ciência, Tecnologia e Ensino Superior

Alzheimer’s disease (AD) affects as much as 10% of the world population above 65 years of age but after years of research it is still not understood exactly how the disease appears and, even less, how to treat it.

But work just published in The EMBO Journal 1 opens the door to new ways for disease intervention by showing that lipids found throughout the brain can dissolve the large insoluble protein plaques characteristic of the disease, releasing their soluble protofibrillar components, and also that it is the soluble components and not the insoluble plaques that provoke neural death.

These results identify a new target for disease intervention – the soluble protofibrillar components – but also alert for the fact that the insoluble plaques are, nevertheless, reservoirs of toxicity and so will need to be controlled too, while also identifying a totally new influence in the disease – the patients’ lipid metabolism – and in this way add a few important pieces to the puzzle that is AD.

Alzheimer’s is a progressive fatal illness that results from the death of certain brain areas associated with cognitive functions such as memory and learning. Starting with forgetfulness as the disease progresses patients suffer major personality changes and, eventually, a terrifying loss of the “self” occurs. The disease is associated with an abnormal amyloid-beta (Ab) protein that incapable of fold properly –all proteins need specific 3D structures to work properly – accumulates instead in large insoluble deposits (or amyloids) in the brain of patients exactly where neurons’ death occurr. These insoluble plaques have a fibrillar structure and originate from the agglomeration of free Ab-peptide after an intermediate state as soluble protofibrills.

Although initially it was thought that the large fibrillar plaques were behind the disease, more recent research seems to suggest that it is the intermediate protofibrillar form that is neurotoxic. Also recently there has been increasing suggestions of a link between AD and alterations in the lipid metabolism of patients, while some lipids – such as cholesterol – have been shown to affect the formation of the insoluble plaques.

Trying to understand better what is happening in the disease Ivo Cristiano Martins, Inna Kuperstein, Joost Schymkowitz, Frederic Rousseau and colleagues at the VIB Switch Laboratory, Vrije Universiteit Brussel, and the VIB Department of Molecular and Developmental Genetics,K.U.Leuven, Belgium decided to test the effect of different biological lipids on both the protofibrillar and the fibrillar forms of the aberrant Ab-protein, while also analysing how all these factors affected the neurodegeneration characteristic of AD.

To start, the team of researchers exposed insoluble fibrillar plaques like those found in patients’ brains to several naturally occurring lipids – such as cholesterol – to find that in their presence the plaques partially dissolved, releasing the soluble protofibrills that constitute them. This result showed, for the first time, that the formation of plaques was a reversible process and as such could be manipulated if necessary.

Martins, Kuperstein and colleagues then tested the neurotoxicity of the obtained protofibrills and show that they were able, not only of kill isolated neurons, but also of affect the brain of injected mice. The insoluble fibrills (plaques) were shown to be biologically inert on both cases. To further investigate the different neurotoxicities of the fibrillar versus the protofibrillar form of Ab-peptide, mice were injected with one or the other and tested for memory and learning capacities (both cognitive capabilities affected in Alzheimer’s). Again it was found that only the protofibrillar form deteriorated mice capabilities to perform. Interestingly, the damaging effect was temporary agreeing with the idea that the protofibrills eventually turned into the inert fibrillar plaques in a process similar to what occurs in AD.

Martins, Kuperstein and colleagues’ work has several important implications. Their results confirm that it is the protofibrillar form of Ab-peptide that is neurotoxic and not the insoluble fibrillar plaques but also reveals - by showing that plaque formation is reversible - that the plaques are, nevertheless, reservoirs of toxicity. They also suggest that disturbances in the metabolism of lipids have the potential to influence the development of AD and may be the reason behind the fact that many times the extension of the insoluble plaques in the brain of AD patients does not correlate with their disease severity.

As Ivo Martins – a Portuguese researcher and one of the main authors explains - “before our work the plaques were seen as relatively innocuous, the last stage of the disease, but what we show here is that they are in reality a” time bomb” ready to be activated by interacting with lipids”

A major implication of Martins and colleagues’ work is to bring into the field two very exciting new avenues for disease intervention: control of the lipid metabolism and neutralization of the toxicity/formation of Ab protofibrills. And, in a world where Alzheimer's affects about 10 percent of people over 65 with as much as half of those over 85 suffering with the disease, new targets for therapy are undoubtedly good news. As Martins reveals “The next step, already under work in the our laboratory, is the production of drugs and /or antibodies capable of control the neurotoxic fibrils.”

Piece researched and written by Catarina Amorim – Catarina.Amorim at linacre.ox.ac.uk

Catarina Amorim | alfa
Further information:
http://www.nature.com/emboj/journal/v27/n1/full/7601953a.html

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: 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 >>>