Fig. 1.

Proteomic measurements of amyloid and tau align with region-specific neuropathological burden.A, schematic representation of the experimental workflow for matched human brain tissue samples across regions BA6 and BA37 from 109 ROSMAP cases that were enzymatically digested with trypsin into peptides and individually labeled with isobaric tandem mass tags (TMT) followed by LC-MS/MS. Log₂ abundances were normalized as a ratio divided by the central tendency of pooled standards (global internal standards, GIS) and median centered. Protein abundances were analyzed using differential and co-expression methods. B, TMT-MS quantified APP normalized abundance is significantly increased in AsymAD and AD cases compared to Control. One-way ANOVA (BA6: F = 7.987, p > 0.001; BA37: F = 9.469, p > 0.001) with Tukey’s multiple comparisons test. C, TMT-MS quantified MAPT normalized abundance is significantly increased in AD. One-way ANOVA (BA6: F = 3.522, p < 0.05; BA37: F = 12.69, p > 0.001) with Tukey’s multiple comparisons test. D, APP normalized abundance and CERAD scores positively correlate in each brain region. Biweight midcorrelation (Bicor) and p value (BA6: bicor = 0.46, p = 4.6e-07; BA37: bicor = 0.482, p = 1.1e-07). Best-fit line for each region is determined by a linear model, and confidence interval is shaded around line. E, MAPT normalized abundance and Braak scores positively correlate in BA37. Bicor and p value (BA6: bicor = 0.13, p = 0.17; BA37: bicor = 0.37, p = 8.2e-05). Best-fit line for each region is determined by a linear model, and confidence interval is shaded around line. ∗p < 0.05, ∗∗∗p < 0.005, ∗∗∗∗p < 0.001; F, F value; Bicor, biweight midcorrelation. AD, Alzeimer’s disease.