Figure 1
From: Mechanisms that lessen benefits of β-secretase reduction in a mouse model of Alzheimer’s disease
Beneficial effects of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1) haploinsufficiency on memory deficits and β-amyloidosis decline in 5XFAD mice with advanced age. Mice at (a) 6 months (MO) and (b) 15–18 months of age were trained with two conditioned stimulus/unconditioned stimulus pairings for contextual fear conditioning. 5XFAD mice show significantly lower levels of contextual freezing than wild-type mice irrespective of age when tested 24 h after training (*P<0.05). BACE1+/−·5XFAD mice are rescued completely back to wild-type control levels of contextual memory at 6 months but not at 15–18 months of age (#P<0.05 versus age-matched 5XFAD); n=10–19 mice per group. (c) Brain sections were immunostained with the 6E10 anti-Aβ antibody. Shown are representative photomicrographs of the hippocampus and cortical area. Scale bar=500 μm. Percentage area occupied by amyloid-β (Aβ) deposits in the hippocampus (d) and cerebral cortex (e) was measured for quantification (n=4 mice per group). Note that BACE1 haploinsufficiency is no longer able to significantly reduce profound plaque burden in 5XFAD mice with advanced age (*P<0.05 versus age-matched 5XFAD controls). The Aβ load at 15–18-month-old 5XFAD mice with or without BACE1+/− mutation is significantly greater than that of 6-month-old 5XFAD mice (#P<0.05). All data are presented as mean±s.e.m.
