Figure 1

Representative images showing increased β-secretase (BACE1) immunoreactivity (IR) at selected vascular sites, in addition to neuritic plaques, in the human brains with amyloid deposition relative to controls. Panels (A-F) are montages of low magnification images showing BACE1 (A-C) and 6E10 [reactive to Aβ, potentially to β-amyloid precursor protein (APP) and APP β-C-terminal as well] (D-F) IR over the subiculum (Sub), hippocampus (CA sectors) and dentate gyrus (DG) between adjacent sections from two cases with brain amyloid pathology (A,B,D,E) and one control (C,F). In the second case (B,E), vascular BACE1 and 6E10 labeling (arrows) is evident at low magnification. In the control case, no staining is seen with 6E10 labeling (F, with tissue lamination illustrated by toluidine counterstain). Note that the BACE1 IR at the mossy fiber terminal field is comparable in (A-C). Panels (G-J) show low magnification views of BACE1 IR in the temporal neocortical grey and white matter from two additional brains, with a diffuse neuropil pattern in the control (G,H) and increased labeling in the amyloid case at selected vascular profiles (I.J). Confocal double immunofluorescence shows a partial colocalization of BACE1/6E10 IR among typical neuritic plaques (K-N), with the structures exhibiting overlapped labeling (appearing yellow) representing dystrophic neurites (M,N). A capillary profile exhibiting weak BACE1/6E10 IR is also seen in the field (M, N). Scale bar in (A) = 2.5 mm, applying to (B-F), equivalent to 500 μm for (G-J), 200 μm for (K-M) and 50 μm for (N).