Effects of a combination of BACE1 haploinsufficiency and neprilysin overexpression on β-amyloidosis in 12-month-old 5XFAD mice. (A) Brain sections were immunostained with the 6E10 anti-Aβ antibody. Shown are representative photomicrographs of the hippocampal and cortical regions. Scale bar = 500 μm. (B, C) Percentage area occupied by Aβ deposits in the hippocampus (B) and cerebral cortex (C) was measured for quantification (n = 2–5 mice per group). (D, E) Levels of total Aβ42 in guanidine extracts (D) and soluble Aβ oligomers (E) were quantified by sandwich ELISAs and expressed in nanograms and picograms per milligram of total protein, respectively (n = 4–6 mice per group). Significant and equivalent reductions in all Aβ measurements are observed in NEP · 5XFAD and BACE1+/− · NEP · 5XFAD mice. #
p < 0.05 vs. 5XFAD. All data are presented as mean ± SEM.