Figure 1. Decreased Aβ secretion in AD-transgenic (Tg) but not wild-type (WT) neurons with time in culture. A, Levels of Aβ1–40 and Aβ1–42 were assayed by ELISA in media of AD-transgenic or wild-type neurons. While wild-type neurons secrete comparable amounts of Aβ peptides at 12 and 19 DIV (n = 6; left), AD-transgenic neurons showed decreased levels of Aβ1–40 and Aβ1–42 in media at 19 compared with 12 DIV (n = 10; *p < 0.05, **p < 0.01; right). B, Levels of intraneuronal Aβ42 were increased by 46 ± 17% in AD-transgenic neurites at 19 compared with 12 DIV (n = 4; p < 0.05). C, D, Levels of intraneuronal Aβ42 were unchanged in wild-type neurons at 19 compared with 12 DIV, as quantified by confocal immunofluorescence (C) and ELISA (D) (n = 4). E, Left, Levels of αCTFs were decreased by 52 ± 2%, while levels of βCTFs and full-length APP were unchanged in AD-transgenic neurons at 19 compared with 12 DIV (n = 4; p < 0.01). Right, Levels of αCTFs were decreased by 32 ± 9% (n = 5; p < 0.05), while levels of βCTFs (longer exposure) showed a trend for a 49 ± 16% decrease (p = 0.074) in wild-type neurons at 19 compared with 12 DIV. F, At 19 DIV, AD-transgenic neurons failed to enhance secretion of both Aβ1–40 and Aβ1–42 during g-LTP (n = 6, right). In contrast, wild-type neurons were still able to increase Aβ1–40 and Aβ1–42 secretion during g-LTP (n = 4; *p < 0.05, left). Conc., Concentration. Scale bars, 50 μm.