Questions Over Beta-Amyloid May Have Alzheimer’s Treatment Ramifications

the Psychiatry Advisor take:

New research is questioning the shape and composition of the structures that form beta-amyloid plaque — the hallmark of Alzheimer’s disease — that could have implications for how drugs are designed that tackle the formation of the plaque.

Researchers at the Institute for Research in Biomedicine, Barcelona, Spain, examined abeta fibrils, the structures that first form in the brain when beta-amyloid protein start to clump together. More specifically, they looked at Abeta 40 and Abeta 42, the two most common forms of Abeta. Abeta 42 is the most common variant found in Alzheimer's.

Currently, Alzheimer’s researchers use a technique called SDS-PAGE to analyze the beta-amyloid clumps. But the Spanish researchers say this methodology is flawed because of incorrect conclusions it makes about the shapes of protein and the number of molecules they have.

Because of the belief that Abeta 42 formed mainly of pentamers and hexamers, it was thought that these formed "beta-sheets," which drugmakers have been focused on tackling. However, using mass spectrometry, the Spanish researchers discovered that  both Abeta 40 and Abeta 42 form dimers, trimers and tetramers and that  they are spherical and lack a defined structure, they reported in the journal Scientific Reports.

They add that the assumption that drugs have to interfere with the beta-sheet structure in order to target the clumping of beta-amyloid in Alzheimer’s should be reconsidered, and recommend caution when using SDS-PAGE to study Abeta.