Chronic brivaracetam or ethosuximide do not alter amyloid precursor protein metabolism or reduce synapse loss in APP/PS1 mice. Thirteen-month old APP/PS1 mice were treated with brivaracetam (Briva) (A–C) or ethosuximide (ETX) (D–F) as in Figure 5 and then analyzed for soluble amyloid-β (Aβ) levels (A, D), Aβ plaque density (B, E) or dentate gyrus PSD-95 synaptic area (C, F). An Aβ enzyme-linked immunosorbent assay showed no effect of brivaracetam (A) or ethosuximide (D) on total Aβ monomers (P > 0.05 by Student’s t-test), and cortical and hippocampal deposits of Aβ plaque were not different between treatment groups (Student’s t-test) (B, E). Synaptic puncta were quantified in the molecular layer of the dentate gyrus by immunohistochemistry. Drug therapy did not reverse synapse loss seen in APP/PS1 mice (P > 0.05 by analysis of variance with post hoc comparisons). + Indicates drug therapy; - indicates vehicle. n.s., Not significant; WT, Wild type.