Spreading pattern of phosphorylated tau-positive granular glial pathology in the cerebral white matter of patients with multiple system atrophy

Multiple system atrophy (MSA) is a major neurodegenerative disorder characterized by phosphorylated α-synuclein-positive oligodendroglial cytoplasmic inclusions. The presence of phosphorylated τ-positive granular glia (pTGrG) in the cerebral white matter and putamen has recently been reported, and it has been suggested that pTGrG pathology may be a common pathological feature of MSA. However, its spreading pattern and relationship with clinical features remain unclear. We examined the spreading pattern of pTGrG pathology and the clinical factors associated with it. The middle frontal, precentral, and middle temporal gyri, as well as the inferior parietal lobule and occipital lobe were histopathologically examined in 14 patients with clinicopathologically confirmed MSA. A distinct spreading pattern of pTGrG pathology was revealed, initially detected in the precentral white matter and subsequently extending to the parietal, frontotemporal, and occipital white matter. The severity of pTGrG pathology significantly correlated with disease duration and tracheostomy duration, but was not associated with any clinical MSA subtype or with dementia. The findings suggest that pTGrG is a common pathological feature of MSA with a unique spreading pattern, and with correlations to duration of disease and tracheostomy, thereby highlighting its potential as a biomarker for disease progression.