01 and P < 0.05 for the comparison with three- and six-month-old counterparts, Bonferroni t-test). Tone fear memory of nTg mice was not affected by age (F(1,41) = 0.3, NS, ANOVA, simple effects). selleck chem inhibitor Of interest is that the significant dissociation between age-dependent onset of the impairment in the context and tone memory was caused by stronger tone memory of nTg mice as compared to the strength of their context memory at each age (t(13) = -2.8, P < 0.02; t(16) = -2.4, P < 0.05; t(12) = -2.7, P < 0.02, for three, six and 12 month tests, respectively). The tone and context memory of CRND8 mice were comparable (Figure ?(Figure1B1B and ?and1C1C right panel).

A?? plaque burden increases with age in CRND8 mice We previously demonstrated that amyloid plaque burden was significantly correlated with sodium dodecyl sulfate (SDS-) soluble and formic acid (FA-) extractable A?? fractions in the CRND8 model, and that both biochemical and histo-pathological analyses of A?? led to the same interpretations of cognitive impairment in multiple memory systems [24]. The representative pictures of the A?? plaque burden in the brain of three-, six-, and 12-month-old CRND8 mice are shown in Figure ?Figure2.2. The A?? plague burden increased with age (rS = 0.94, P < 0.001), differentiating the age cohorts of CRND8 mice (F(2,26) = 100.6, P < 0.001, Figure ?Figure3).3). Post-hoc comparisons revealed differences in A?? burden between all tested age groups (3 < 6 < 12, Ps < 0.01, Bonferroni t-test, Figure ?Figure3A).3A).

A?? burden at younger ages was most prominent in the cortical, hippocampal, and amygdala regions (Figure 2AB); at 12 months the A?? deposits were observed in the whole brain, including thalamic, hypothalamic and caudate/amygdala regions (Figure ?(Figure2C).2C). We found a strong positive correlation between the A?? plaque burden evaluated by staining with pan A?? 1-16 antibody and the total number of A?? dense core deposits stained by anti- A??40 antibody (rS = 0.9, P < 0.001). Consequently, the dense-core A?? burden is not reported. Figure 2 Representative images of A?? deposits, stained with pan A?? 1-16 (33.1.1) antibody, in the brain sections of (A) three-, (B) six-, and (C) 12-month-old CRND8 mice. The total amyloid burden in the combined areas of cortex, hippocampus and ... Figure 3 Amyloid-?? plaque burden and conditioned fear memory in CRND8 mice.

(A) The levels of amyloid-?? burden (mean (%) ?? SEM) significantly increased in CRND8 mice between the ages of three and 12 months. The progressing with age A?? … Batimastat Increase in A?? plaque burden impairs context and tone fear memory The increased-with-age selleck inhibitor levels of A?? plaque burden were correlated with the impairment in context and tone fear memory in CRBD8 mice (rS = -0.43, P < 0.05 for context (Figure ?(Figure3B),3B), and rS = -0.40, P < 0.05 for tone (Figure ?(Figure3C)3C) memory).