BACE1 is elevated in 5XFAD transgenic mouse brain, with highest concentrations surrounding amyloid plaques.

Abstract

<p>(A) Hemibrains from 6 month old 5XFAD (+) mice (n = 17), and non-transgenic (Tg) (–) age-matched controls (n = 13) were homogenized and 20 µg/lane of protein were subjected to immunoblot analysis for transgenic human (h) APP, BACE1, Aβ, and βIII-tubulin as a loading control. (B) hAPP and BACE1 immunosignal intensities were normalized to those of βIII-tubulin and displayed as percentage of non-Tg control. Note that 5XFAD mice have significantly elevated levels of BACE1 and Aβ compared to non-Tg controls, as detected by BACE1 antibody clone 3D5 and human APP/Aβ antibody clone 6E10, respectively. Bars represent SEM, asterisks (*) indicate significant changes compared to non-Tg control, p<0.001***, (C) Coronal brain sections from 5XFAD mice were co-stained with anti-BACE1 antibody (red) and Thioflavin S (green) for fibrillar amyloid and imaged by fluorescence microscopy. At low magnification, high levels of BACE1 (red) are readily observed in mossy fibers of the hippocampus, which is the normal localization pattern of BACE1 in the brain (BACE1, first row). At high magnification, BACE1 (red) is shown to concentrate abnormally in an annulus that immediately surrounds the fibrillar amyloid plaque core (green; cortex, second row; hippocampus, third row). Scale bars = 1 mm, first row; 100 µm, second and third rows.</p

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