Once the deconvolution approach was optimized, we calculated the cell proportion in AD cases and controls from the different brain regions of Mayo and MSBB datasets. The RNA-seq data for the Mayo Clinic study (n = 191) [18] and MSBB (n = 300) [39] are deposited in the AMP-AD knowledge portal (synapse ID: syn5550404 and syn3157743; Table 1). The Mayo study includes RNA-seq from the TC and CB for AD affected and non-demented controls, in addition to pathological aging (PA) participants (Fig. 1). The MSBB also profiled four additional cerebral cortex areas: APC; STG; PGH; and IFG; Table 1 and Fig. 1). We restricted the case-control analysis to subjects with definite AD and autopsy-confirmed controls. In addition, we generated RNA-seq from parietal lobe for participants of the Knight-ADRC (84 late-onset cases, carriers of genetic risk factors and 16 controls; Additional file 1: Table S1) and The Dominantly Inherited Alzheimer Network (DIAN; 19 carriers of mutations in APP, PSEN1, PSEN2) (Table 1; Fig. 1). We employed the same pipeline to process all of the samples in order to avoid any bias.