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We examined the ultrastructural localization of beta/A4 protein in cerebellar diffuse plaques (DP) in three Alzheimer's disease brains by the indirect immunoperoxidase technique. Intense immunoreaction products were scattered in the DP; they were strongly suggested to be located between small cell processes. Reaction products were dot-like and/or amorphous, and occasionally fibrillar. Adjacent semithin sections of regions immunoreactive for beta/A4 protein revealed only very small amounts of amyloid fibrils between cell processes and/or small numbers of degenerating neurites. The small degenerating neurites which appeared in most DP lacked paired helical filaments (PHF) and neurofilaments (NF). These findings suggest that the majority of the beta/A4-immunoreactive substance in cerebellar DP is non-fibrillar pre-amyloid found between cell processes and barely detectable by routine electron microscopy.
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