Bridges, L. R.

In the last seven years, cryo-EM maps of neuropathological fibrils from Alzheimer\'s disease and other neurodegenerations have been released by various authors. The first publication noted an unknown component coordinating with lysine residues in the protein, a finding recapitulated in many succeeding studies. Previous authors have emphasized difficulties in analysing this component, but current findings, using powerful visualisation software UCSF ChimeraX on all publicly available maps, indicate that the issue is tractable. Lysine-coordinating extra densities have common features, including a Y-shaped substructure, suggestive of a molecular factor in common, in neuropathological fibrils from a wide range of neurodegenerations and involving misfolded proteins beta-amyloid, alpha-synuclein, prion protein, tau and transmembrane protein 106B. A similar component, albeit in non-lysine environments, was found in neuropathological fibrils involving TAR DNA-binding protein 43 and TATA-binding protein-associated factor 15. The results suggest the existence of a common molecular factor, a predominantly anionic polymer, linking these diseases and raising the possibility of a unitary basis for Alzheimer\'s and other neurodegenerations. Based on evidence here, RNA is a feasible candidate for this putative common factor. Such findings raise the possibility of new diagnostic tests and treatments for these devastating diseases in the future.