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Figure 3 | BMC Neurology

Figure 3

From: Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal β-amyloid deposition in the human brain

Figure 3

Correlative morphometric characterization of BACE1 and 6E10 immunoreactivity (IR) in intracortical arterioles in confocal fluorescent preparation. Panels (A-C) show colocalized BACE1/6E10 IR in the endothelia (arrows), with a ring-like Aβ deposition (arrowhead) in the smooth muscle layer that is not colocalized with BACE1 IR. Panels (D-F) demonstrate an arteriole containing BACE1 labeled neurites and local Aβ deposition (arrowheads) in the vascular wall, with BACE1 IR colocalizing with 6E10 IR inside but not outside swollen process-like elements (arrows). Panels (H-J) show a vessel with densely packed Aβ products in the wall, with BACE1 IR over the same area comparable to background. Fusiform bisbenzimide (Bis)-labeled nuclei appear lost in the middle layer of arterioles in (D/E, G/H) relative to (A/B). A typical neuritic plaque (NP) consisted of BACE1 labeled dystrophic neurites and Aβ deposits is also seen in (G-I). Panels (J) plots the mean optic densities (o.d.) of BACE1, 6E10 and bisbenzimide fluorescence measured over the wall of individual normal [i.e., amyloid negative (-), 10/brain)] and amyloid [i.e., amyloid positive (+), 20/brain] arterioles from five individual brains, with the area of interest (AOI) illustrated as the purple-line circled areas in (D/E and G/H, and also in Figure 4A to demonstrate the method to measure densities at normal control vessels). Note the increase of BACE1/6E10 o.d. and reduction of bisbenzimide o.d. in the amyloid (+) relative to (-) arterioles. Panel (K) shows a correlative densitometric analysis by sorting the order of individual vessels (n = 100 from 5 brains) according to their elevated levels of 6E10 densities relative to baseline (defined as 100%, mean of densities reported from all non-amyloid vessels). BACE1 density increases initially in parallel with that of 6E10 IR, but tends to reduce among most profiles as 6E10 IR further increases. Bisbenzimide density tends to decline with the increase of 6E10 labeling. Scale bar = 50 μm in (A) applying to (B,C,G-I), equivalent to 100 μm for (D-F).

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