Fig. 5

TMEM106B overexpression leads to age-related downregulation of immediate early genes. We performed bulk RNAseq on the cerebral hemibrain of 15-month-old animals (hTMEM106B(+) and wild-type (n = 4/genotype). A Volcano plot and B heatmap of differentially expressed genes using DESeq2. C STRING-DB Interaction network of DEGs shows clear interaction between most DEGs, which are well-known immediate early genes (IEGs). D Pathway enrichment analysis using Enrichr shows enrichment of the DEGs in neurotrophic tyrosine receptor kinase (NTRK) signaling. E Visual representation of the NTRK signaling pathway, highlighting the involvement and function of the identified DEGs in the pathway. Figure created with Biorender. F qPCR validation of top three differentially expressed genes across different age groups (n = 4–7/genotype) shows that there is no difference in expression in 1-month-old animals. The downregulation of IEGs is becoming apparent at 6 months of age with a significant downregulation of Arc in hTMEM106B(+) mice, which further progresses in a significant decrease in 12-month-old animals and 15-month-old animals. This data shows that the downregulation of IEGs is age-related and not present from birth. Data represented as mean ± SEM. Two-way ANOVA *, P < 0,05; **, P < 0,01