Supplementary Figure 1 Supplementary Figure 1. The burdens of Aβ, CAA and tau in the brains of 12-month-old female and male wild type mice. (A): There was no congophilic or 6E10-positive plaque in the brains of female (left panels) and male (right panels) wild type mice. Scale bar denotes 1mm. (B): There was no CAA observed in the brains of wild type mice, no matter female or male, detected by 1A4 and 6E10 double-immunofluorescence. Scale bar denotes 5μm. (C): Representative images (up panel) and quantification (down panel) of pS396-tau immunohistochemical staining in the neocortex of female and male wild type mice (n=11 per sex, mean±s.e.m., Student’s t-test). There was no difference of tau pathology between female wild type mice and male wild type ones. n.s. denotes no significant difference. Scale bar=100μm. Supplementary Figure 2. Supplementary Figure 2. Astrocytosis and microgliosis in 12 month-old female and male wild type mice. (A) and (B): Representative images (A) and quantification (B) of astrocytosis detected by GFAP immunohistochemical staining in the hippocampus and neocortex of female and male wild type mice aged 12 months (n=11 per sex, mean±s.e.m., Student’s t-test). There was no difference in astrocytosis between female wild type mice and male wild type ones. n.s. denotes no significant difference. Scale bar=1mm. (C): Representative images of astrocytosis in the neocortex of different groups. Compared with wild type, there was a significant increase in the number and size of astrocytes in APP/PS1 transgenic mice. Scale bar=100μm. (D) Representative images of microgliosis detected by CD45 immunohistochemical staining in the hippocampus and neocortex of female and male wild type mice aged 12 months. There was rarely a detectable CD45-positive cell in the brains of both female and male wild type mice. Scale bar=1mm. Supplementary Figure 3. Supplementary Figure 3. Neuron number and synapse-associated protein expressions in the brains of 12-month-old female and male wild type mice. (A) and (B): Representative images and quantification of NeuN-positive neurons in the CA1 region of hippocampus and neocortex of female and male wild type mice (n=11 per sex, mean±s.e.m., Student’s t-test). Scale bar denotes 100μm. (C): Representative western blot images of PSD-95, VAMP-1 and SNAP-25 expression in brain homogenates of 12-month-old female and male wild type mice. (D): Quantification of PSD-95, VAMP-1 and SNAP-25 levels by western blotting (n=11 per sex, mean±s.e.m., Student’s t-test). n.s. denotes no significant difference.