Alzheimer's assemblies identified

Assemblies of twelve units of the protein amyloid-beta42 are a probable key neurotoxic agent in the development of Alzheimer's disease, according to a study online in Nature Chemistry this week. The identification of such a key toxic species could pave the way for treatments that specifically target the disease in its early stages of development.

Plaques, formed from large assemblies of amyloid-beta proteins, are known to form as a result of Alzheimer's disease, but recent evidence suggests that the disease symptoms are caused by small assemblies ― oligomers ― of the protein. However, a variety of investigations into how these oligomers arise have provided conflicting results.

Michael Bowers and co-workers used a technique called electrospray-ionization ion-mobility mass spectrometry to study the mixture of oligomers formed by amyloid-beta42 and some closely related proteins that do not result in disease. The technique allowed the researchers to study both the mass and the geometry of oligomers formed. Although all the proteins studied formed these small assemblies, only amyloid-beta42 went on to form one that contained twelve units.

In an accompanying News & Views article, David Clemmer and Stephen Valentine say 'One can imagine using the insight gained here to design interventions that are designed to arrest oligomer growth at a specific size.'

doi: 10.1038/nchem.247

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