Breaking up (amyloid) is hard to do

Abstract

Gandy and Heppner discuss the implications of a new animal study on our understanding of the pathogenesis and treatment of Alzheimer disease.

Figure 1. A Large Energy Barrier Prevents Rapid Redissolution of Fibrillar Amyloid

In this issue of PLoS Medicine, Borchelt and colleagues demonstrate in the living amyloid-laden mouse brain that Aβ plaques are cleared very slowly, even if synthesis of new Aβ precursor molecules is extinguished using a tet-off system [7]. In the recent, relevant, but independent, X-ray crystallography study [8], Nelson et al. envisioned the free-energy plot shown above as a graphic description of the kinetics of transition from monomeric Aβ to fibrillar Aβ (ΔG_formation). For the reverse reaction, Nelson et al. envision the ΔG_dissolution as the large free-energy barrier to spontaneous solubilization of amyloid fibrils. Presumably, it is this ΔG_dissolution that underlies the slow disappearance of brain plaques in the Borchelt study in transgenic mice. (Illustration: Sapna Khandwala, adapted from [8])