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Additional file 2: Supplemental Table 1. Top 25 genes classifying the eight distinct astrocyte clusters identified in scRNAseq analysis of E3 and E4 mouse brains (clusters visualized in Fig. 1e). Supplemental Table 2. Age, sex, and APOE genotype of cognitively normal individuals according to Ε4 carriage and age cohort (young = 18–39, middle-aged = 40–65). Values represent means +/− (SD). Supplemental Table 3. Clinical characteristics of cognitively unimpaired individuals according to Ε4 carriage and age cohort (young = 18–39, middle-aged = 40–65). Values represent means +/− (SD). Ca, Caucasian; AA, African American; His, Hispanic; A, Asian; BMI, body mass index. Supplemental Table 4. Plasma metabolites of study participants analyzed by gas chromatography – before and after a dietary glucose challenge. Supplemental Table 5. Pre-screening checklist. A response of “yes” to any of the following resulted in exclusion from the study. Supplemental Fig. 1. Cluster cell counts. Number of cells in each graph-based cluster from all cells (a), and astrocytes only (b). Bars represent mean number of cells in each cluster, with the number of E3 cells (circles) and E4 cells (squares) noted by symbols. Supplemental Fig. 2. APOE expression in single-cells and specific astrocyte clusters. (a) UMAP visualization of E3 (left) and E4 (right) cells showing expression of APOE. APOE expression is primarily limited to cells identified as astrocytes. (b) Expression of APOE in astrocyte-only UMAP (Aldoc + cells). Inset shows the 8 distinct astrocyte clusters. (c) Violin plots showing expression of APOE in all astrocytes (left) and within each astrocyte cluster (right). (**P