Background: Semantic variant primary progressive aphasia (svPPA) is generally sporadic, with very few reports of tau pathology caused by MAPT mutations.
Methods: A 64-year-old man was diagnosed with svPPA with MAPT P301L mutation. Clinical information, cognitive and language functions, multimodal magnetic resonance imaging (MRI), blood biomarkers, fluorodeoxyglucose (FDG) imaging and tau positron emission tomography (PET) were obtained.
Results: Semantic memory impairment was the earliest and most prominent symptom in this family. Tau accumulation and hypometabolism were observed prior to brain atrophy in mutation carriers. Plasma NfL and GFAP concentrations were elevated in the two svPPA patients. Some relative decreases and some relative increases in regional cerebral blood flow (CBF) as measured by arterial spin labelling (ASL) were observed in mutation carriers compared to noncarriers.
Conclusions: This study describes a large svPPA-affected family with the MAPT P301L mutation and provides an ideal model for inferring underlying pathology and pathophysiological processes in svPPA caused by tauopathies.
Keywords: Frontotemporal lobar degeneration; MAPT gene; Next-generation sequencing; P301L mutation; Semantic variant primary progressive aphasia.
© 2023. The Author(s).