Cartoon depicting seeding of PrP conversion by fibrils of various sizes in injected scrapie brain homogenate. Following inoculation larger fibrils (green) might diffuse poorly in brain but would seed PrP conversion (orange) locally near inoculation site. Smaller oligomeric fibrils (blue) may be too small to seed PrP conversion , but can travel by diffusion and in brain interstitial fluid (ISF) flow towards blood vessel basement membranes where they might be bound by glucosaminoglycans (GAGs) and other molecules. These concentrated oligomers might form a scaffold capable of seeding new PrPres generation (orange) which in turn might self-scaffold further PrPres conversion (orange) extending both radially and linearly around blood vessel. Smaller oligomers generated at this new site might travel in the ISF flow to new blood vessels and might initiate seeding at these distant sites.