We initially ascertained the effect of APOE ε4 on the cell-type composition. We observed a significant lower relative proportion of neurons (β = − 0.06 for each of the ε4 alleles; p = 9.91 × 10−03) and increase of relative proportion of astrocytes (β = 0.10; p = 4.15 × 10−02) from the TC included in the Mayo Clinic dataset (Additional file 1: Table S10; Fig. 4a; Additional file 1: Figure S9a). This finding was replicated when we performed a multi-area analysis of the MSBB dataset (β = − 0.04; p = 2.60 × 10−03 and β = 0.05; p = 1.31 × 10−03 for neurons and astrocytes, respectively; Table 4; Fig. 4a; Additional file 1: Table S10; Additional file 1: Figure S9a). Given the strong risk conferred by the APOE ε4 allele [4], we studied its effects on the cell-type composition by restricting our analysis to AD brains. We observed a significant association in the multi-area analysis of the MSBB dataset (β = − 0.03 p = 4.01 × 10−02; Table 4; Fig. 4b; Additional file 1: Table S11;
