NACP/alpha-synuclein immunoreactivity in diffuse neurofibrillary tangles with calcification (DNTC)

Area of Science:

• Neuroscience
• Neuropathology
• Dementia Research

Background:

• Diffuse neurofibrillary tangles with calcification (DNTC) is a rare dementia characterized by tau pathology without amyloid deposition.
• Alpha-synuclein (alphaS) accumulation is implicated in various neurodegenerative disorders.

Purpose of the Study:

• To investigate the presence and extent of alpha-synuclein (alphaS) deposition in Diffuse neurofibrillary tangles with calcification (DNTC) brains.
• To explore the relationship between alphaS pathology and tau pathology in DNTC.

Main Methods:

• Immunohistochemistry was used to examine eight DNTC brains.
• Specific antibodies targeted alpha-synuclein (alphaS) and neurofibrillary tangles.

Main Results:

• Remarkable alphaS deposition was observed in neurons and astrocytes across multiple brain regions.
• Lewy bodies and Lewy neurites were prevalent in the amygdala, hippocampus, substantia nigra, and dorsal vagal nucleus.
• Numerous alphaS-positive astrocytes were found in the hippocampus and temporal cortex.

Conclusions:

• DNTC exhibits significant alphaS pathology, involving both neurons and astrocytes, alongside its primary tau pathology.
• These findings indicate a potential shared pathophysiological basis between DNTC and synucleinopathies like Parkinson's disease and dementia with Lewy bodies.
• An interaction between alphaS and tau pathology, independent of amyloid, is suggested in DNTC.