Rapamycin inhibits mTOR and decreases Aβ₄₂ levels in brains of PDAPP mice.

<p><b>a, b and f</b>, representative immunoblots of whole brain lysates from control- and rapamycin-treated PDAPP transgenic and non-transgenic littermate mice; <b>c, g–k</b>, quantitative analyses of protein or phosphoprotein levels. <b>a–c</b>, Levels of phosphorylated (activated) p70 were decreased in brains of rapamycin-treated non-transgenic (<b>a</b>) and transgenic PDAPP (<b>b</b>) mice (<b>c</b>, **, <i>P</i> = 0.006 and *, <i>P</i> = 0.01 respectively). <b>d</b>, rapamycin did not alter Aβ₄₀ levels but significantly decreased soluble Aβ₄₂ levels in the brains of transgenic PDAPP mice *, <i>P</i> = 0.02. Homogenates were measured at 100 mg brain tissue/ml. <b>e</b>, rapamycin did not alter levels of endogenous mouse Aβ₄₀ levels in brains of non-transgenic mice. Aβ₄₂ levels were below the detection limit of the ELISA (not shown). <b>f</b>, representative immunoblots of PDAPP mouse brain extracts. <b>g–k</b>, Quantitative analyses of APP, C99 and C83, NEP and IDE immunoreactivity in lysates of brains from control- and rapamycin-treated PDAPP mice. Data were normalized to β-actin levels. Student's <i>t</i> test was used to determine significance of differences between means. Data are means ± SEM.