Primary progressive aphasia with glial cytoplasmic inclusions

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Neuroimaging

Background:

• Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by gradual language decline.
• Typical neuropathological findings in PPA include tauopathies or TDP-43 proteinopathies affecting cortical neurons.
• The current case presents atypical neuropathological features distinct from previously described PPA subtypes.

Observation:

• An 80-year-old woman with a 3-year history of PPA showed cerebral atrophy and hypometabolism in left frontal and temporal lobes on CT, MRI, and SPECT.
• Temporal lobe biopsy revealed Gallyas-positive intracytoplasmic inclusions in glial cells, resembling those in multiple system atrophy.
• These inclusions contained hyperphosphorylated tau (p-tau) and ubiquitin, with minimal neuronal tau pathology and absence of other common neurodegenerative markers.

Findings:

• The neuropathological examination identified glial intracytoplasmic inclusions with hyperphosphorylated tau.
• These inclusions differed significantly from the neuronal pathology typically observed in primary progressive aphasia.
• The observed glial pathology shared similarities with inclusions found in multiple system atrophy.

Implications:

• This case suggests a potential novel subtype of primary progressive aphasia characterized by glial tau inclusions.
• The findings expand the spectrum of tauopathies and their clinical manifestations in neurodegenerative disorders.
• Further research is needed to elucidate the pathogenesis and clinical significance of this glial tau pathology in PPA.