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We examined the ultrastructural localization of β/A4 protein in cerebellar diffuse plaques (DP) in three Alzheimer's disease brains by the indirect immunopcroxidase 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 β/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 β/A4-immunoreactive substance in cerebellar DP is non-fibrillar pre-amyloid found between cell processes and barely detectable by routine electron microscopy.