Occurrence of human alpha-synuclein immunoreactive neurons with neurofibrillary tangle formation in the limbic areas of patients with Alzheimer's disease.

We examined alpha-synuclein immunoreactivity in the brains from 23 patients with Alzheimer's disease (AD) and two patients with Down's syndrome. In ten of the 23 AD cases and both the two Down's syndrome cases, alpha-synuclein immunoreactivities were observed in the neurons of the limbic areas, predominantly of the amygdala. Nearly all alpha-synuclein-positive neurons had tau-positive neurofibrillary tangles (NFT) in the same neurons, and these consisted of intermingled-type and superimposed-type. By immunoelectron microscopy, the intermingled-type revealed aggregations of alpha-synuclein-positive filamentous components, which were in continuity with paired helical filaments (PHF), while the superimposed-type revealed accumulations of alpha-synuclein-positive non-filamentous components in PHF bundles. These findings suggest that alpha-synuclein can accumulate in PHF and form filamentous aggregations in neurons of the limbic areas in AD cases.