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Additional file 4: Figure S4. Tamoxifen-induced reduction of astrocytic APOE4 in cortical regions with and without CAA/plaques. a, Representative images of X34 for amyloid plaques/CAA, APOE, GFAP+ astrocytes, and IBA1+ microglia. Arrowhead: APOE in astrocyte. Arrow: APOE in microglia. Scalebar: 50 µm. b, Percentage of APOE coverage in cortical regions with CAA, plaques, or without CAA/plaques. c, d, Ratio of APOE in GFAP+ astrocytes (c) or IBA1+ (d) microglia area coverage normalized to CAA/plaque load. ∆ = males, ○ = females. Data expressed as mean ± SEM, student’s t-test (two-sided) performed for all statistical analyses except (b – no plaques, CAA, plaques), (c – no plaques, CAA, plaques), and (d – no plaques, CAA), where Welch’s t-test was performed. *P < 0.05, **P < 0.01. No other statistical comparisons are significant unless indicated.

Additional file 3: Figure S3. Increased CAA and reduction of amyloid plaques in the subiculum albeit no change in overall amyloid. a–d, X34 staining for fibrillar plaques/CAA (a) with percent area coverage of total X34 (b), CAA (c), and amyloid plaques (d) in the dorsal subiculum of 10-month-old 5X+AL- or 5X+AL + mice after astrocytic APOE4 removal at 2-months-of-age. e, Proportion of CAA in total X34+ staining. Scalebar: 300 µm. ∆ = males, ○ = females. Data expressed as mean ± SD, student’s t-test (two-sided) performed for all statistical analyses except (b), where Welch’s t-test was performed. **P < 0.01, ***P < 0.001. No other statistical comparisons are significant unless indicated.

Additional file 1: Figure S1. No sex differences in APOE4 mRNA expression and protein concentrations in mice with or without Cre expression. a, Relative expression of APOE mRNA normalized to beta-actin in cortex. b, c, PBS-soluble and guanidine-HCL-soluble (“insoluble”) APOE protein concentrations assessed by ELISA from cortex. Data expressed as mean ± SD, two-way ANOVA, Sidak’s multiple comparisons test performed for all statistical analyses. No statistical comparisons are significant unless indicated.

Additional file 6: Figure S6. Characterization of morphological responses of GFAP+ astrocytes to CAA or plaques. a, Representative reconstruction of GFAP+ astrocytes around CAA or amyloid plaques using Simple Neurite Tracer. b–f, Morphological analyses of GFAP + astrocyte size (Convex Hull analysis) (b), number of processes (c), total processes length (d), number of branching points (e), and mean process length (f). Scalebar: 50 µm. ∆ = males, ○ = females. Data expressed as mean ± SD, two-way ANOVA, Sidak’s multiple comparisons test performed for all statistical analyses. *P < 0.05, **P < 0.01. ***P < 0.001. No other statistical comparisons are significant unless indicated.

Additional file 5: Figure S5. No change in GFAP+ astrocyte coverage in the subiculum. a, b, GFAP staining for astrocytes (a) with percent area coverage of total GFAP immunoreactivity (b) in the dorsal subiculum of 10-month-old 5X+AL- or 5X+AL + mice after astrocytic APOE4 removal at 2-months-of-age. Scalebar: 300 µm. ∆ = males, ○ = females. Data expressed as mean ± SD, student’s t-test (two-sided) performed for all statistical analyses. No statistical comparisons are significant unless indicated.

Additional file 2: Figure S2. No sex differences in amyloid or Aβ pathology in mice with or without Cre expression. a–c, X34 staining for fibrillar plaques/CAA with percent area coverage of total X34 (a), CAA (b), and amyloid plaques (c) in the cortex overlying the hippocampus of 10-month-old 5X+AL- or 5X+AL+ mice after astrocytic APOE4 removal at 2-months-of-age. d–f, Aβ immunoreactivity (Aβ-IR) with percent area coverage of total Aβ-IR (d), vascular Aβ-IR (e), and plaques (f) in the cortex overlying the hippocampus. Data expressed as mean ± SD, two-way ANOVA, Sidak’s multiple comparisons test performed for all statistical analyses. No statistical comparisons are significant unless indicated.

Additional file 2: Supplementary Fig. 2. Comparisons between MRV purified and unpurified stocks. A ��� C, Stocks were created from in vivo passage and collection of 7 day post neonatal infection thymi and were used directly (MRV Stock) or semi-purified (MRV Purified). BALB/c mice were mock- or MRV-infected with MRV Stock or MRV Purified via i.p. injection on P0 then were evaluated by flow cytometry for percent CD4+ cells per total CD3+ cells from the spleen at 7dpi (A) or weight at 7dpi (B). C, Copies of MRV DNA per mL of stock were evaluated by qPCR.

Additional file 1: Supplementary Fig. 1. Peripheral, neonatal MRV infection in 5XFAD mice does not accelerate A�� plaque burden. A, Schematic of experimental paradigm (6 mpi). B, C, Percent of CD4+ and CD8+ T cells in plasma 10 dpi (B) or 6 mpi (C). D, E, HJ3.4B+ immunostaining for A�� plaque load in the cortex. F���I, Staining and quantification for Tau5+ total tau (F, G) and AT8+ phosphorylated tau in the cortex (H, I). J, Schematic of experimental paradigm (6 wpi). K, L, Percent area HJ3.4B+ A�� immunoreactivity (A�� - IR) in cortex. Dpi: days post infection. Mpi: months post infection. Wpi: weeks post infection. p-tau: phosphorylated tau. Scale bar: 500 ��m. Data expressed as mean �� SEM, student���s t-test (B, C, E, G, J, M). No statistical comparisons are significant unless indicated.

Additional file 3: Supplementary Fig. 3. Effects of acute, intrahippocampal MRV infection on tau pathology. A, Schematic of experimental paradigm. B ��� G, Staining and quantification for Tau5+ total tau (B, C, D) and AT8+ phosphorylated tau in the cortex (E, F, G). p-tau: phosphorylated tau. Scale bar: 500 ��m. Data expressed as mean �� SD, student���s t-test. *P