Deep proteome profiling of the hippocampus in the 5XFAD mouse model reveals biological process alterations and a novel biomarker of Alzheimer’s disease

Deep hippocampal proteomic analysis of 5XFAD mice

5XFAD transgenic mice develop AD pathogenesis rapidly in their brains, with amyloid plaques appearing in the hippocampus beginning at 3–4 months of age⁵. To quantify the amyloid plaques deposited in the hippocampus of 5XFAD mice at 5 and 10 months of age, we performed immunohistochemistry using the biotin-4G8 antibody to stain amyloid plaques. At 5 months of age, we observed a few small amyloid plaques in the hippocampus of these model mice. At 10 months of age, the amyloid plaques were increased in both size and number (Supplementary Fig. S1). To investigate the neurodegeneration-associated hippocampal proteome in response to amyloid pathology, we analyzed the hippocampi of 5XFAD mice at 5 and 10 months versus those of wild-type mice.

We performed quantitative proteomic analysis using three replicates of hippocampi dissected from…