Ultrastructure of the neuropil threads in the Alzheimer brain: their dendritic origin and accumulation in the senile plaques

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Abstract
Summary Thread-like structures immunoreactive with paired helical filaments and tau antisera were demonstrated as mesh-works in the neocortices of five brains with Alzheimer-type dementia, but not in those of five normal aged control brains. The ultrastructure of the threads was examined using paired routine electron microscopic ultrathin sections and adjacent 0.4-μm-thick semithin sections, immunostained for β protein. Outside the β protein-positive senile plaques, neuropil threads appeared sporadically as small slender neurites, containing either regularly constricted or straight filaments. These neurites often showed dendritic profiles. Similar threads were also seen within the senile plaques. The threads were accumulated in amyloid fibril-rich primitive plaques, but not in amyloid fibril-poor diffuse plaques. The presence of these threads was closely associated with neurofibrillary tangle formation. Our findings suggest that wide-spread change of the neuropil neurites, neuropil threads or curly fibers, both outside and inside of the senile plaques are dendritic in origin and play an important role in the clinical manifestation of dementia.