ASSOCIATION OF VASCULAR AMYLOID-BETA AND CELLS OF THE MONONUCLEAR PHAGOCYTE SYSTEM IN HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS (DUTCH) AND ALZHEIMER-DISEASE

Arterial and arteriolar amyloid-beta (A beta) deposition in hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) and Alzheimer disease (AD) cerebral amyloid angiopathy (CAA) were studied as to morp hology, extent, and association with mononuclear phagocyte system (MPS ) cells using A beta, a-smooth muscle actin, and monocyte/macrophage m arker (HLA-DR, CD68, CD11c, CD45) immunohistochemistry. The HCHWA-D/AD arterial/arteriolar media showed compact A beta deposits, first appea ring at the media/adventitia junction, and concomitant smooth muscle l oss. Only HCHWA-D CAA featured (a) severe involvement of larger arteri es and (b) arterioles showing a single or double ring of radial A beta surrounding compact A beta. Radial A beta appeared to develop at the media/adventitia junction. Monocyte/macrophage marker-positive foci/ce lls co-localized with HCHWA-D arterial A beta. Focal HLA-DR/CD11c posi tivity was observed at the media/adventitia junction of AD/HCHWA-D art eries in the absence of local A beta, but not in controls. Monocyte/ma crophage marker positivity co-localizing with radial A beta appeared c ontinuous with perivascular cells and microglia clustering perivascula rly. These results suggest that (a) MPS cells are topographically asso ciated with HCHWA-D arterial A beta and radial arteriolar A beta, and (b) HLA-DR/CD11c immunoreactivity may appear at the media/adventitia j unction prior to A beta. The latter finding and the assumed formation of radial A beta at the media/adventitia junction may relate to involv ement of the abluminal basement membrane in CAA pathogenesis. The role of MPS cells in this process remains to be established.