Tau immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy

Area of Science:

• Neuroscience
• Neuropathology
• Cell Biology

Background:

• Multiple System Atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs), which are ubiquitinated structures in oligodendroglia.
• The role and nature of tau protein expression within GCIs in MSA remain unclear.
• Understanding tau in GCIs is crucial for differentiating MSA from tauopathies like progressive supranuclear palsy (PSP).

Purpose of the Study:

• To investigate the presence and significance of tau protein expression in GCIs within MSA lesions.
• To compare tau expression patterns in MSA GCIs with tau pathology observed in oligodendroglial coiled bodies (CBs) in PSP and corticobasal degeneration.

Main Methods:

• Immunohistochemical analysis of pontine nuclei lesions from 10 MSA cases.
• Utilized antibodies targeting various tau protein epitopes (N-terminal, C-terminal, tau-2, tau-1 after dephosphorylation).
• Correlated tau-immunoreactivity in GCIs with ubiquitin-positive GCIs and neuronal preservation.

Main Results:

• Tau-2 was consistently, albeit weakly, detected in 28.6–66.7% of ubiquitinated GCIs across all MSA cases.
• Tau-2 immunoreactivity in GCIs did not correlate with GCI density or neuron counts.
• N-terminal and C-terminal tau antibodies did not label GCIs; tau-1 showed occasional positivity post-dephosphorylation.
• GCIs exhibited distinct tau epitope profiles compared to CBs in PSP/corticobasal degeneration, which show broader tau epitope involvement.

Conclusions:

• Tau expression in MSA GCIs is limited and primarily involves specific epitopes (tau-2), suggesting it's not integral to the core neurodegenerative process.
• The observed tau expression in GCIs is likely a response to non-specific cellular stress in oligodendroglia, contrasting with the direct tau pathology in 'tau diseases'.
• This finding helps distinguish the molecular pathology of MSA from other neurodegenerative disorders involving tau.