Fig. 6: Proteomic signatures of cognitive aging phenotypes.
From: Midbrain extracellular matrix and microglia are associated with cognition in aging mice
a Schematic of behavioral classification and proteomic analysis. Young-adult (4 months; n = 12; black triangles) and late-middle-aged (18 months; n = 24; gray triangles) male and female mice were tested on open field, novel object recognition, and T Maze tasks. Schematic created in in BioRender. Gray, D. (2025) https://BioRender.com/h5muudq. Data from all 3 behaviors were used to perform hierarchical clustering analyses to delineate young-average (black), aging-unimpaired (AU; green), and aging-impaired (AI; yellow) mice. Midbrain tissue from behaviorally-classified mice then underwent subcellular fractionation followed by proteomic analysis. b PCA plots of all core matrisome proteins from membrane, cytoskeletal, and insoluble fractions. c PCA plot of extracellular matrix proteoglycans from the membrane fraction (left). Average protein intensities of extracellular matrix proteoglycans in the membrane fraction separated by age and cognitive status (middle; n = 6 young, n = 5 middle-aged unimpaired, n = 7 middle-aged impaired mice). Aging mice exhibited higher proteoglycan abundances (n-Way ANOVA; two-sided; p = 0), and aging-impaired mice showed higher proteoglycan abundances compared to aging-unimpaired mice (p = 0.021; post-hoc Tukey-Kramer). Right: heat plot of extracellular matrix proteoglycan abundances in the membrane fraction and bar plots of their relationship with cognitive status and age (*p < 0.05; linear probability model). d PCA plot of synapse proteins from the membrane fraction (left). Average protein intensities of synapse proteins in the membrane fraction separated by age and cognitive status (n-Way ANOVA; two-sided; p = 0.62; n = 6 young, 5 middle-aged unimpaired, 7 middle-aged impaired mice). Right: heat plot of glutamate receptor abundances and bar plots of their relationship with cognitive status and age (* p < 0.05; linear probability model). In all boxplots, boxes represent interquartile ranges (IQR; 25–75 percentiles), middle lines represent medians, and whiskers extend ± 1.5*IQR. Source data are provided in the file Source Data - Fig. 6 and all statistics are provided in Supplementary Data 6. * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001 for each statistical test.
