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. 2022 Sep 20;2(9):837–850. doi: 10.1038/s43587-022-00281-1

Fig. 2. C1q deletion blunts proteomic changes in P301S synapses.

Fig. 2

a, Experimental design of hippocampal PSD proteome analysis. Hippocampi from 6- and 9-month-old male mice were dissected and isolated synapse fractions were analyzed by TMT multiplex proteomics (Methods). b, Venn diagram showing the number of identified proteins and overlap between synapse proteomes in the 6- and 9-month cohort from this study and synapse proteome from 9-month-old female mice described previously3. c, Percentage of DE proteins in the indicated genotype comparisons at 6 and 9 months. d, A heat map showing z scores across genotypes for proteins that were DE between C1qKO and WT mice (regardless of P301S genotype) (P ≤ 0.05; FC ≥ 5). e,f, Volcano plots showing the comparison between P301S versus WT and P301S;C1qKO versus WT synapse proteomes at 6 and 9 months. MSstats was used to calculate log2FC and standard error utilizing a linear mixed-effects model that considered quantification from each peptide and biological replicate per protein. P values were then calculated by comparing the model-based test statistic to a two-sided Student’s t-test distribution. Significantly up- and downregulated proteins (P < 0.05, log2FC ± 0.5) are shown in blue and red circles, respectively. Selected DE proteins are labeled with their protein or gene name. g, Selected up- or downregulated KEGG pathways in P301S versus WT and P301S,C1qKO versus WT synapse proteomes at 6 and 9 months. Only DE proteins were included for pathway analysis.

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