Fig. 1

Workflow of the study. After brain tissue preparation of all 32 sample fractions, we performed mass spectrometry using SWATH (data-independent acquisition), followed by differential protein abundance analysis using MSqRob (quantitative protein-level statistical inference). The identified proteins with differential abundance in SD patients (P-value < 0.01 and ± 0.3 log2 fold change) were subjected to four parallel analyses (green boxes). The results of three analyses – Gene Ontology, protein–protein interactions, and comparison to other proteomic datasets – were integrated in a protein network, enabling collective interpretation of the main findings. Additionally, we compared the differential proteome of SD to proteins known to interact with TDP-43 and to proteins identified in TDP-43 neuronal aggregates based on previously published work (Laferrière et al., 2019). Abbreviations: SD = semantic dementia; LCM = laser capture microdissection; LC–MS/MS = Liquid chromatography with tandem mass spectrometry; AD = Alzheimer’s disease; FTD = frontotemporal dementia; TDP-43 = TAR DNA-binding protein 43