Fig 1: Amyloid plaque pathology, biomarkers of neurodegeneration and neuroinflammation. a Amyloid plaques were measured by segmentation and registration to the CCFv3 atlas post-methoxy-X04 labeling. N = 4-30 mice/ group. b Methoxy-X04 positive plaque density across brain regions in the AppSAA KI/KI. Hippocampal F. = formation. N = 4-6 mice/ group. c 3D heatmaps show brain distribution of methoxy-X04 positive plaques in AppSAA KI/KI at 8-month-old. Except panel i, all panels from d-n show data from 8-month-old mice. d Representative images of brain sections show Aß plaque immunoreactivity in AppSAA KI/KI but not in KI/+ mice. Leptomeningeal cerebral amyloid angiopathy is indicated by arrows. e Confocal images from AppSAA KI/KI stained for plaques, microglia markers (Iba1, CD68), dystrophic neurites (AT8), neurofilament (Nf) and lysosomal marker (LAMP1). Far right column provides a magnified view of the inset in merged images. Scale bars = 10 µm. f-g Quantification of brain areas covered by Aß plaques (f) and AT8 area (g). N = 3-6 mice/ genotype. h Total tau levels in CSF. N = 6-11 mice/ genotype. i Higher level of CSF Nf-L in aged AppSAA KI/KI relative to +/+ mice. N = 4-33 mice/ group. Age: F (4, 111) = 61.74, P < 0.0001. Genotype: F (1, 111) = 33.46, P < 0.0001. j-l Quantification of Iba1 (j), CD68 (k), percentage of the Iba1 and CD68 signals overlapping with plaques (l). N = 3-6 mice/ genotype. m TREM2 levels measured in brain homogenates. N = 10 mice/ genotype. n Differential abundance (log2) of cytokines measured in brain lysates. N = 10 mice/ genotype. Bars represent 95% confidence intervals of fold change. Graphs from f-m are box and whisker plots. P values: (f, j, k) one-way ANOVA with Dunnett’s multiple comparison test, (g, h, m) t-test. Each genotype compared to AppSAA +/+; **P < 0.01, ***P < 0.001 and ****P < 0.0001