Figure 4

Sites of focal and early inflammation show BACE1 upregulation in neurons. (A) Representative confocal immunostaining of CD11b positive microglia and BACE1 and GFAP and BACE1 in 3 month old APP transgenics showed that BACE positive neurons were found close to focally activated microglia cells in 3 month old APP [V717I] mice. (B) Quantitation of the number of BACE1 positive cells in relation to the distance to CD11b or GFAP positive cells. (C) Representative image of focal GFAP expression, BACE1 activity and overlay in APP [V717I] mice at 3 m of age. (D) Measurement of BACE1-activity was calculated as percentage of 3 month old controls (wt 3 m) and showed that enzyme activity was already elevated in APP [V717I] mice at 3 month (tg 3 m) (n = 5, ANOVA followed by a TUKEY test, *p < 0.05). (E) RT-PCR detection of BACE1 mRNA levels of cortical (frontal cortex, FC) and cerebellar (Cb) lysates from wild type controls (wt), APPV [7171I] (tg) mice at 3 (3 m) and 16 months (16 m). (F) Densitometrical analysis and quantitation of BACE1 mRNA levels of frontal cortex lysates of APP [V717I] transgenic and controls at the respective age (n = 6, ANOVA followed by a TUKEY test, *p < 0.05). Bar graphs are = 50 μm for CD11b/neuN and GFAP/BACE and = 25 μm for CD11b/BACE1).