Clinical characteristics of semantic variant of primary progressive aphasia with TDP-43- and tau-related gene variants.

Abstract

Background: Semantic variant primary progressive aphasia (svPPA) can be inheritable. There is a predictable relationship between the pathological substrate and genetic variants in this condition.

Objective: To report a case with svPPA who carried a MAPT gene mutation and to explore clinical differences between svPPA with TDP-43 pathology-related genes and svPPA with tau pathology-related genes.

Methods: Studies reporting svPPA patients with MAPT, TARDBP, GRN, C9orf72, or TBK1 gene mutations were selected from PubMed and China National Knowledge Infrastructure (CNKI). Of the 109 articles from the literature, 31 reports involving 75 cases provided the outcomes of interest.

Results: Along with the new case, 76 patients (43 males and 33 females) were included in this study. Among them, 34 carried MAPT mutations, 15 with TARDBP mutations, 13 with GRN mutations, 8 with C9orf72 expansions, and 6 with TBK1 mutations. The analysis results revealed that the mean age of onset in the tau pathology-related gene mutation group (50.56 ± 7.46 years) was younger than that in the TDP-43 pathology-related gene mutation group (58.19 ± 7.66 years) (p < 0.001). MAPT and TARDBP mutations were more prevalent in the study population, accounting for 44.7% and 19.7%, respectively. Within the MAPT gene mutation population, P301L accounted for 41.2%, while IVS10 + 16C > T accounted for 38.2%. Among the TARDBP gene mutation carriers, I383V accounted for 73.3%.

Conclusions: The onset age in svPPA patients with tau pathology-related gene mutations is younger than in those with TDP-43 pathology-related gene mutations. MAPT variants, specifically P301L and IVS10 + 16C > T, as well as TARDBP I383V variant, may have higher mutation frequency in svPPA.