Figure 2.

PPARγ-mediated degradation of Aβ is dependent on induction of ApoE through the stimulation of LXR and PPAR pathways. Primary wild-type microglia (A) or astrocytes (B) were treated for 24 h with pioglitazone or DMSO followed by the addition of soluble Aβ₄₂ (2 μg/ml) for 24 h. The cells were pretreated with antagonists for PPARγ (T0070907, 10 nm) or LXR (22S hydroxycholesterol, 10 μm) for 2 h. Intracellular Aβ was measured by ELISA. apoe knock-out microglia (C) or astrocytes (D), or wild-type microglia (E) or astrocytes (F) were pretreated for 24 h with DMSO or drug, followed by the addition of soluble Aβ₄₂ and exogenously supplied apoE (1 μg/ml) or apoA1 (2 μg/ml). Remaining intracellular Aβ was measured using ELISA. These data are represented as a percentage of DMSO-treated control samples (mean ± SEM, Student's t test, *p < 0.05, **p < 0.01, ***p < 0.001, n ≥ 3). Cortical homogenates obtained from PPARγ conditional knock-out animals were analyzed by Western blot analysis for ABCA1, apoE, and actin (G) and quantified (H) (mean ± SEM, Student's t test, *p < 0.05, ***p < 0.001, n ≤ 6 animals per genotype).