α-synuclein-positive structures in association with diffuse neurofibrillary tangles with calcification

alpha-Synuclein is known to be a major constituent of the Lewy bodies (LBs) in Parkinson's disease (PD) and the neuronal and glial cytoplasmic inclusions (NCIs, GCIs) in multiple system atrophy. alpha-Synuclein-positive inclusions such as LBs, NCIs and GCIs sometimes show colocalization with tau-positive neurofilaments. Studies using alpha-synuclein immunohistochemistry have often found LBs in the amygdala of patients with familial or sporadic Alzheimer's disease (AD), as well as in patients with Down's syndrome and AD. However, no studies have reported alpha-synuclein-positive structures in cases of diffuse neurofibrillary tangles with calcification (DNTC), which is characterized by numerous neurofibrillary tangles (NFTs) throughout the cerebral cortex but few, if any, senile plaques. We investigated the distribution of alpha-synuclein-positive structures in two cases of DNTC: a 65-year-old woman (brain weight, 850 g) and a 75-year-old woman (brain weight, 800 g). In both cases, severe cerebral atrophy predominant in the temporal lobe was noted. Microscopically, alpha-synuclein-positive intracytoplasmic inclusions and neurites were found in the superior temporal lobe (within the temporal pole), amygdala, parahippocampus, entorhinal cortex and insula, the regions most affected by the NFTs. alpha-Synuclein-positive intracytoplasmic inclusions were rare or absent in other regions of the cerebral cortex and brainstem. This distribution pattern differs from that of PD or dementia with LBs. Our findings suggest that the accumulation pattern of alpha-synuclein is a pathological feature of DNTC, and that DNTC is associated with accumulation of both tau and alpha-synuclein.