Figure 6.

Aβ production, neurogenesis, proneural gene products, and β-catenin signaling in GPC progeny from APP23 vs. WT mice at 12 and 24 months of age. (a-c). Aβ ELISAs of neocortical samples from 12- and 24-month-old APP23 and WT mice revealed that total Aβ levels (a), Aβ₄₀ levels (b), and Aβ₄₂ levels (c) were significantly higher in the APP23 mice than in the WT mice, and the Aβ levels increased with age in the APP23 mice.(Student’s t test, *p < 0.05, **p < 0.01, n = 3 per group). (d). After 2 days in differentiation medium, immunostaining showed a reduced number of newborn neurons (DCX⁺) among the progeny of GPCs (labeled with DAPI) from APP23 mice at 12 and 24 months of age compared to age-matched WT mice. (e). Quantification of the immunoreactive structures revealed a significant reduction in the percentage of newborn neurons among the APP23 progeny compared to age-matched WT progeny (Student’s t test, *p < 0.05, **p < 0.01, n = 3 per group). (f). After 7 days in differentiation medium, the expression levels of the proneural gene products Ngn 2, Mash1, and neuroD1 were reduced in the GPC progeny from 12- and 24-month-old APP23 mice compared to those from age-matched WT mice (n = 3 per group). (g). After 7 days in differentiation medium, non-phosphorylated β-catenin levels decreased and both GSK-3β and phosphorylated β-catenin levels increased in the GPC progeny of 12 and 24-month-old APP23 mice compared to age-matched WT mice; however, no significant changes in the levels of Wnt3 or frizzled were observed (n = 3 per group). Scale bar represents 50 μm.