Figure 6

Characterization of BACE1 elevation in meningeal cells associated with leptomeningeal amyloidosis. Panel (A) shows BACE1 labeled cells aligning along the pia mater in a case with cerebral amyloid angiopathy with prominent leptomeningeal amyloidosis (B), in contrast to a control case wherein no BACE1 and Aβ (6E10) labeling is present at the pia (C,D). Arrows in (A,B) points to profiles with increased BACE1 and 6E10 IR over the background. Panel (E) shows a preparation of leptomeninge sample from the temporal lobe (E), which are rinsed thoroughly in cold phosphate buffer for biochemical analysis (F). Levels of BACE1 protein and C99 in leptomeningeal lysates are elevated in 5 cases with CAA relative to 5 control cases (G,H), as is BACE1 enzymatic activity measured in the lysates (H). Aβ42 levels are also higher in the CAA group relative to control (H). In primary cell culture of leptomeningeal biopsies, meningeal cells appear polygonal under phase contrast microscope (J), co-express fibronectin (FN) (K) and BACE1 (L). These cells also express the β-amyloid precursor protein (APP) (H, the corresponding FN labeling image is not shown). Scale bar = 250 μm in (A) applying to (B-D), equivalent to 50 μm for inserts in (A,B), 25 μm for (J) and 12.5 μm for (K-M).