Ageing‐related tau astrogliopathy severely affecting the substantia nigra

Aims Astrocytic tau pathology is a major feature of tauopathies and ageing‐related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement. We aimed to identify cases with prominent astrocytic tau pathology in the SN. Methods We use the term nigral tau‐astrogliopathy (NITAG) to describe cases showing an unusually high density of ARTAG with less neuronal tau pathology in the SN. We collected clinical information and studied the distribution of tau pathology, morphological features and immunostaining profiles in three cases. Results Three cases, all males with parkinsonism, were identified with the following clinicopathological diagnoses: (i) atypical parkinsonism with tau pathology reminiscent to that in postencephalitic parkinsonism (69‐year‐old); (ii) multiple system atrophy (73‐year‐old); (iii) traumatic encephalopathy syndrome/chronic traumatic encephalopathy (84‐year‐old). Double‐labelling immunofluorescence confirmed co‐localization of GFAP and phosphorylated tau in affected astrocytes. Staining profiles of NITAG revealed immunopositivity for various phosphorylated tau antibodies. Some astrocytic tau lesions were also seen in other brainstem regions and cerebral grey matter. Conclusions We propose NITAG is a rare neuropathological feature, and not a distinct disease entity, in the frame of multiple system ARTAG, represented by abundant tau‐positive astrocytes in various brain regions but having the highest density in the SN. The concept of NITAG allows the stratification of cases with various background pathologies to understand its relevance and contribution to neuronal dysfunction. Astrocytic tau pathology is less common in the grey matter of the brainstem. We identified three unique cases with prominent nigral tau‐astrogliopathy (NITAG). NITAG was defined by an unusually high density of tau pathology in astrocytes (A‐C, D‐F, G‐I in three cases) as compared with neurons, predominantly in the substantia nigra, associated with various primary diseases that might have contributed to clinical parkinsonism. The concept of NITAG helps to understand the development of neuronal dysfunction without prominent neuronal tau pathology.