Diffuse neurofibrillary tangles with calcification (DNTC) is a rare tangle-predominant dementia, as well as one of the tauopathies lacking Aβ deposition. It is characterized by temporo-frontal lobar atrophy, Fahr-type calcification and, histopathologically, numerous neurofibrillary tangles in the limbic system and neocortex. Recently, accumulation of α-synuclein (αS), the precursor of the non-β amyloid component (NAC) of Alzheimer's disease, has been shown in diverse neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, multiple system atrophy and parkinsonism-dementia complex of Guam. To clarify whether αS accumulates in other neurodegenerative disorders, we investigated eight DNTC brains using immunohistochemistry and demonstrated remarkable αS deposition in the neurons and astrocytes in many anatomical regions. Abundant Lewy bodies were observed in the amygdala (seven cases) and hippocampus (seven cases), and, to a lesser degree, in the substantia nigra (six cases) and dorsal vagal nucleus (five cases). In the hippocampus, many Lewy neurites were distributed in the stratum oriens and stratum pyramidale in the CA2-3 and the subiculum. Furthermore, numerous NAC-positive astrocytes were detected in the hippocampus and temporal cortex. This investigation reveals that neurons and astrocytes are extensively involved in remarkable αS pathology in the DNTC brain, and that the αS pathology compounds the cardinal pathological features of tau pathology. These findings suggest that (1) DNTC shares a common pathophysiological background with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy in which abnormal αS aggregation is observed, and (2) there is an interaction between αS and tau pathology that does not involve amyloid in DNTC.
- Diffuse neurofibrillary tangles with calcification
- Non-β amyloid component
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Cellular and Molecular Neuroscience