Schematic diagram of proteopathic strain formation. Pathogenic proteins are most likely to misfold from an unfolded or partially folded state. The path to a given strain is influenced by such factors as sequence differences, truncation of the protein, post-translational modifications, and the milieu in which the seeds form and propagate. As the molecules acquire excess β-sheet, they bind to one another and multimerize into small oligomers, protofibrils, and/or amyloid fibrils. In addition to their influence on disease presentation, different molecular strains are sometimes reflected in the presence, distribution, and/or morphology of resultant lesions in the brain.