Fig. 2. Identifying an incipient AD proteomic signature.

(A) Proportional odds models to identify an incipient AD proteomic signature. Comparing AD and CN individuals in BLSA and ROS, we identified an AD proteomic signature as 120 unique proteins across the ITG and MFG (FDR P < 0.10). Two-way intersection significance was determined using SuperExactTest (P < 0.00001). We then analyzed these 120 proteins in YAPS to establish an incipient AD proteomic signature (25 proteins in red) as the overlap across all three cohorts. Three-way intersection significance was determined using SuperExactTest (P < 0.00001). (B) Proteins in BLSA and ROS defining the 120 protein AD proteomic signature. Pink dashes indicate FDR P = 0.10. The black vertical line represents no difference in protein concentration between AD and CN. A total of 1300 proteins are presented; gray points indicate proteins that do not meet the FDR threshold. Blue and red points indicate proteins significantly lower and higher, respectively, in AD individuals in both cohorts. (C) AD proteomic signature proteins overlapping with proteins differentially abundant in YAPS (the 25-protein incipient AD signature). Pink dashes represent P = 0.05. The 120-protein AD proteomic signature is the background; gray points indicate proteins that do not meet the P value threshold. Blue and red points indicate proteins significantly lower and higher, respectively, in APOE ε4+ individuals. (D) Protein levels of the 25-protein incipient AD proteomic signature (region with lower P value visualized). Y axis indicates log₁₀(OR), with positive values indicating increased protein levels in APOE ε4+ (YAPS) or AD (BLSA and ROS) and negative values indicating lower levels. OR, odds ratio. * indicates opposite direction of abundance in AD/CN between BLSA and ROS.