Distinct cell type-specific protein signatures in GRN and MAPT genetic subtypes of frontotemporal dementia

ABSTRACT: INTRODUCTION: Frontotemporal dementia (FTD) is characterized by progressive atrophy of frontal and/or temporal cortices and considerable clinical, pathological, and genetic heterogeneity. METHODS: Frontal and temporal cortex tissues from FTD-GRN (n=9), FTD-MAPT (n=13), and non-demented controls (n=11) were analysed with quantitative proteomics (DIA). Expression-weighted cell type enrichment deduced the role of major brain cell types and gene ontology analysis identified distinct biological processes. FTD-MAPT data was also compared to an AD (n=10) protein signature. RESULTS: We identified brain region-specific FTD protein expression signatures. In frontal cortex of FTD-GRN, we observed immune processes in endothelial cells and mitochondrial dysregulation in neurons. In temporal cortex of FTD-MAPT, we observed dysregulated RNA processing, oligodendrocyte dysfunction, and axonal impairment. Comparison with AD indicated that alterations in RNA processing and oligodendrocyte function are distinct for FTD-MAPT. DISCUSSION: Our results indicate cell type-specific biological processes distinctive for genetic FTD subtypes. These findings may aid the development of FTD subtype-specific treatment strategies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Suzanne Miedema  

LAB HEAD: August B. Smit

PROVIDER: PXD031419 | Pride | 2022-08-12

REPOSITORIES: Pride