Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) due to microtubule‐associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy
FTDP‐17 follows a pattern of autosomal dominant inheritance with clinical, biochemical and neuropathologic heterogeneity 3. The phenotypes overlap with phenotypes of sporadic primary tauopathies, including progressive supranuclear palsy 6, Pick's disease (PiD) 7, corticobasal degeneration (CBD) 8 and globular glial tauopathy (GGT) 9.
GGT is a newly recognized 4R tauopathy with extensive white matter tau pathology and characteristic glial inclusions, including Gallyas‐positive globular oligodendroglial inclusions (GOI) and globular astrocytic inclusions (GAI). The latter are usually Gallyas‐negative or at most show only weak staining with Gallyas silver method 10. A proposed classification of GGT includes three clinicopathologic subtypes: subtype I with frontotemporal distribution of tau pathology and clinical features of frontotemporal dementia (‘FTD‐type’); subtype II with pyramidal features from motor cortex involvement and corticospinal tract degeneration [‘motor neuron disease (MND)‐type’]; and subtype III with a combination of FTD and MND (‘FTD & MND‐type’) 10.
Here, we compare and contrast clinicopathologic features of five unrelated and three related patients with FTDP‐17 due to p.P301L mutation, including one patient with a GGT phenotype.