Fig. 4: Changes in the structures of proteins that are known to be associated with brain.

A, B Accessibility of 83 labeled peptides that mapped to 62 proteins were significantly changed. The accessibility values in AD groups decreased more steeply than those in NC groups (A). The proteins and peptides corresponding to each change in the accessibility are indicated B. C Expression of 60 brain proteins were compared to averaged expression in six other tissues, as enrichment factor (C). The minimum enrichment factor was 0.13 for Eef2 in NC at 15 months and the maximum enrichment factor was 1232 for Tuba1b in NC at 12 months. Expression of 6 proteins (Eef2, Gucy1b1, NARS1, Slc25a12, Wdr37, Ywhag) was lower in brain than the expression of the corresponding proteins in other tissues at all ages in NC and AD. The bar indicates the enrichment factor, with red indicating an enrichment factor more than 1, and blue indicating an enrichment factor less than 1. Proteins enriched more than 70-fold are marked in red. D, E Two of the three peptides of Cnp share one lysine site, and variations in accessibility for these two peptides are represented. KIIPGSRADF (D) is located at 87-96 amino acid of Cnp and QYQVVLVEPKTAW (E) is located at 141–153 amino acid of Cnp. While they exhibited a decreasing trend in AD, the accessibility values were lower in AD compared to NC, and the trend in AD was steeper than in NC. In the AD group, both peptides showed P-values below 0.05 (Kruskal-Wallis test, p = 0.0084 (D), p = 0.0008 (E)), indicating statistically significant changes in peptide accessibility during AD progression. Experiments were performed in biological triplicates per group, with each dot representing an individual mouse. The significance levels shown in the graph represent P-value from post-hoc analysis (Dunn’s test, adjusted p = 0.0327 for AD 6mo vs. AD 15mo). Blue indicates NC groups, pink indicates AD groups. Asterisk (*) denotes P-value < 0.05 from Dunn’s test. Error bars indicate the mean ± standard deviation. Source data are provided as a Source Data file.