Fig. 2: Inflammatory and microhemorrhagic pathology.

A Lateral and B inferior views of the brain. Black stippling (arrows) in the temporal lobes consistent with petechial hemorrhage is best seen on the inferior view. C A coronal section through the brain shows additional microhemorrhages (arrows). D Methoxy-X04 staining of β-amyloid (blue), phospholipase D3 (green, staining neuronal lysosomes and dystrophic neurites) and Ionized calcium Binding Adaptor molecule 1 or IBA1 (red, staining microglia) shows a neuritic plaque surrounded by dystrophic neurites and activated microglia, 20 µm scale bar. This case met the criteria for moderate Alzheimer’s disease neuropathologic changes. Additional images of β-amyloid deposits in this case are shown in Supplementary Fig. 8. E Longitudinal and F cross-sectional images of penetrating arterioles in the affected region show intensive perivascular inflammatory infiltration and bleeding, stained with hematoxylin and eosin (H&E), 40 µm scale bar in E and 20 µm scale bar in F. A multinucleated giant cell is present at the arrow in E. G Immunostaining for β-amyloid demonstrates inflamed vessels have β-amyloid deposition, 20 µm scale bar. H Cross-sectional and I. longitudinal sections were immunostained for CD68 (Cluster of Differentiation 68), showing numerous macrophages on the inflamed vessels (20 µm scale bar in H and 80 µm scale bar in I); see also Fig. 3. J Serial sectioning through a microhemorrhage enabled visualization of the associated ruptured vessel, 200 µm scale bar. K The ruptured vessel associated with the microhemorrhage contains heavy β-amyloid deposits stained red, vascular marker isolectin in green, blood in non-specific yellowish autofluorescence around the vessel, 200 µm scale bar. L Meningeal whole-mount specimen overlying temporal lobe shows several microaneurysms, 200 µm scale bar. M Meningeal specimen from L stained with thiazine red for β-amyloid (red) and isolectin to label vessels (green) shows severe β-amyloid deposition, including in several microaneurysms (arrrows), 200 µm scale bar. The aneurysm in the white box is shown enlarged in N with a 50 µm scale bar.