Alzheimer's analysed: New clues in brain disease

Amyloid-beta assessed

Recent studies have added weight to the idea that amyloid-beta is a causative agent in Alzheimer's disease rather than the plaques formed from these chunks of misfolded peptide that deposit in the diseased brain. Now, European researchers have used REAPDOR solid-state NMR spectroscopy to analyse the hydrogen bonds in the tiny fibrils of amyloid-beta peptide, offering another perspective on this neurodegenerative disorder.

As populations age so the number of people who will develop Alzheimer's disease increases and the need to find drugs to alleviate the symptoms of this severe dementia becomes more and more pressing and perhaps even stop it in its tracks.

Oleg Antzutkin and researchers at Luleå University of Technology in collaboration with Warwick University in the UK point out that the plaques are more likely a residual artefact of the disease rather than a cause. They have for the first time analysed the hydrogen bonds present in the tiny fibrils of amyloid-beta peptide and suggest that this compound, which is highly toxic to neurons is perhaps the most important form for understanding this debilitating and tragic disease. They point out that amyloid-beta forms small aggregates, oligomers, prior to the formation of peptide plaques and is at its most toxic to brain neurons in laboratory experiments. 

Alzheimer's targets

One aspect of gleaning a clearer understanding of the structure of the oligomers of amyloid-beta peptide would be to provide targets for the design of biological therapeutics, such as antibodies or drugs to eliminate or block these toxic oligomers before they can the kind of damage to neurons that leads to Alzheimer's disease. The researchers now have the technical skills to identify the specific hydrogen bonds in amyloid-beta fibrils that make the supramolecular forms distinct.

REAPDOR

REAPDOR (rotational echo adiabatic passage double resonance) solid-state NMR spectroscopy has succeeded in measuring the distances between nitrogen-15 in the amino groups and oxygen-17 in the carbonyl groups to reveal the presence of hydrogen bonds. Previous methods could not identify these hydrogen bonds. The team has now taken the first step towards full structural characterization of the oligomers, explains Antzutkin.