Until now, the conditions under which this type of protofibril is formed and leads to the disease remained unknown. VIB researchers have now discovered that certain lipids, present also in our brains, promote the formation of this protofibril. This discovery is of major importance because it opens up new avenues of research into finding medicines against Alzheimer's disease. It also explains earlier indications of a link between lipids and Alzheimer's disease.
Misfolded proteins: cause of various diseases
The biological functioning of cells depends on the right folding of thousands of proteins. Normally, cells automatically correct misfolded proteins. In diseases such as Alzheimer’s, Parkinson's and Creutzfeld-Jacob's, however, misfolded proteins are deposited in the body's tissues. In Alzheimer's disease – the most common form of dementia, which in Belgium alone affects about 100,000 people – misfolding of the A -amyloid peptide leads in various stages to the formation of plaques. These plaques consist of accumulations of so-called fibrils and is not in itself toxic. One of the intermediary stages in the formation of plaques is the formation of the protofibril form of the A -peptide. Protofibrils are toxic for brain cells, causing the poisoned cells to die off and leading to memory loss. This is why these protofibrils are considered to be the main cause of the symptoms of Alzheimer's disease.
Surrounding brain lipids destabilize plaques
VIB researchers were able, using certain lipids, to convert the fibrils into protofibrils. This came as a surprise, for it had long been assumed that the fibrils – and the plaque they cause – are stable and that once they have formed they cannot disappear or be transformed into another structure. Ivo Martins, Joost Schymkowitz and Frederic Rousseau (VIB, Vrije Universiteit Brussel), and Inna Kupperstein and Bart De Strooper (VIB, K.U.Leuven) have shown that certain lipids normally occurring in the brain can destabilize the fibrils, and therefore also the plaque that is so typical of Alzheimer's disease. The liberated protofibrils are toxic for brain cells, causing them to die off – at least in vitro. The researchers were able to show that this also happens in vivo by injecting laboratory animals (mice) with the protofibrils. This caused memory loss in the mice. The researchers explain that these symptoms are comparable with those of early stage dementia in humans.
Producing protofibrils for new applications in medicine
The discovery opens up a new avenue of research into possible medicines against Alzheimer's disease. It indicates that substances that neutralize the toxicity or the formation of protofibrils might be able to be used as medicines against Alzheimer's disease. With the discovery of a method for producing toxic protofibrils, the researchers at the VIB have provided a good model for finding medicines that could counteract the formation of protofibrils.
Their research also indicates that the concentration of lipids in the brain greatly influences the biological equilibrium between non-toxic plaques and toxic oligomeres. These results open up new avenues of research into the effects of fat metabolism for diseases such as Alzheimer's.
The research clearly exhibits the advantages to be gleaned from bundling different research groups' expertise. The important results are the fruit of a close collaboration between researchers at the VIB Switch Laboratory, Vrije Universiteit Brussel, and the VIB Department of Molecular and Developmental Genetics, K.U.Leuven.
Sooike Stoops | alfa
Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku
Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy