Are amyloid fibrils molecular spandrels?

•The amyloid fibril structure is accessible to any protein.•The amyloid fibril structure occupies the global free energy minimum.•Amyloid fibrils are a by-product of the evolution of proteins similar to architectural spandrels. Amyloid-β, the protein implicated in Alzheimer’s disease, along with a number of other proteins, has been shown to form amyloid fibrils. Fibril forming proteins share no common primary structure and have little known function. Furthermore, all proteins have the ability to form amyloid fibrils under certain conditions as the fibrillar structure lies at the global free energy minimum of proteins. This raises the question of the mechanism of the evolution of the amyloid fibril structure. Experimental evidence supports the hypothesis that the fibril structure is a by-product of the forces of protein folding and lies outside the bounds of evolutionary pressures.