Poster Abstracts

Introduction: In the past 7 years, cryo-EM maps of fibrils from animal and human neurodegenerations have been published.This represents a novel opportunity to compare and contrast neuropathological structures at the atomic level.Methods: Cryo-EM maps from the electron microscopy data bank (EMDB) were examined in the visualisation software UCSF ChimeraX.This included fibrils from five strains of mouse or hamster scrapie and numerous human neurodegenerations, including Alzheimer's disease (AD), cortical basal degeneration (CBD), chronic traumatic encephalopathy (CTE), Gerstmann-Sträussler syndrome (GSS), multiple system atrophy (MSA) and others.Results: For the neuropathologist, cryo-EM has a distinct advantage over previous structural techniques such as x-ray crystallography.It allows for structural analysis not only of the target protein but, without prior knowledge, other components that might happen to be present.Pathological material ex vivo can be examined, as opposed to chemically purified and crystallised material that might not fully reflect the pathological situation.Accordingly, it is evident that these neuropathological fibrils contain a second unexpected component other than protein, apparently with a structural role, akin to a supporting rod for the stack of protein monomers.Discussion: The nature of the second component is unknown, but the evidence suggests that it is an anionic polymer and RNA is an obvious candidate.Interestingly, this second component is present in infectious (scrapie) and non-infectious (from AD) neurodegenerations, suggesting that the overlap between these types may be narrower than previously supposed.