Using digital deconvolution, we determined the cellular composition for these brains. We observed a significant lower relative proportion of neurons (β = − 0.02, p = 2.66 × 10−02) and significant higher relative proportion of astrocyte in AD (β = 0.03, p = 5.48 × 10−03) for the combined LOAD and ADAD brains compared to controls (Table 3; Fig. 3; Additional file 1: Table S9), consistent with our findings in the Mayo and MSBB datasets. Similarly, the joint analysis of the brains from Knight-ADRC and DIAN showed significant associations between the neuronal and astrocyte relative proportions and neuropathological measures (Braak staging: β = − 0.03, p = 8.51 × 10−06 for neurons and β = 0.03, p = 3.83 × 10−06 for astrocytes; Table 3; Fig. 3b) as well as for clinical measures (CDR: β = − 0.02, p = 2.66 × 10−02 for neurons and β = 0.03 and p = 5.48 × 10−03 for astrocytes; Table 3; Fig. 3c). We did not observe a significant difference in the compositions of microglia or oligodendrocytes (Table 3; Additional file 1: