Using solid-state nuclear magnetic resonance (NMR) spectroscopy, researchers at Luleå University of Technology in collaboration with Warwick University in the UK for the first time in the world managed to analyse hydrogen bonds in tiny fibrils of Amyloid-beta peptide , which probably causes Alzheimer's disease. Thanks to these new results, there is a successful method avaliable - for analysis of structure of Amyloid-beta peptides in their most toxic form, that is, when they are most dangerous for the brain neurons.
- This is a very important step in research on Alzheimer's disease at a molecular level, says Oleg N. Antzutkin, professor in chemistry of interfaces, at Luleå University of Technology.
Until a few years ago scientists believed that amyloid plaques in the brain directly cause Alzheimer's disease. This is because very large amounts of plaques in the brain of Alzheimer´s patients are usually found. Since the activity of our brain is greatest in the regions responsible for short-term memory, there most of the amyloid plaques were found. Here is also usually where Alzheimer's disease is first noticed, in the form of reduced short-term memory. However, it seems to be that Amyloid plaque are rather a residual of something worse.
Now we know that it is a precursor of amyloid plaques, Amyloid-beta peptide that causes nerve cell death in Alzheimer's patient's brain. When Amyloid-beta, forms small aggregates, oligomers, ie before the peptide clumps together into plaques, it is as most toxic to brain neurons. This has been shown in test tube experiments.
However, the molecular structure of these tiny oligomers of Amyloid-beta peptide, is yet unknown today. Therefore, it is difficult to design antibodies or drugs to hit the right targets and be able to eliminate or block these toxic oligomers, before they cause Alzheimer's disease.
A successful method to solve these molecular structures has not been availiable, until now:
- Now we have a method, which can be employed to identify the specific hydrogen bonds in Amyloid-beta fibrils and therefore to distinguish between different supramolecular structures of Amyloid-beta fibrils. Previous methods have not been able to directly probe these hydrogen bonds. Using our method, it will soon be possible to study hydrogen bonds in key fragments of toxic oligomers that will assist solving their supramolecular structures. What we managed to do now, is an important step towards the full structural characterization of oligomers, says Oleg N. Antzutkin.