title: Association of vascular amyloid beta and cells of the mononuclear phagocyte system in hereditary cerebral hemorrhage with amyloidosis (Dutch) and Alzheimer disease.
abstract: 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 morphology, extent, and association with mononuclear phagocyte system (MPS) cells using A beta, a-smooth muscle actin, and monocyte/macrophage marker (HLA-DR, CD68, CD11c, CD45) immunohistochemistry. The HCHWA-D/AD arterial/arteriolar media showed compact A beta deposits, first appearing at the media/adventitia junction, and concomitant smooth muscle loss. Only HCHWA-D CAA featured (a) severe involvement of larger arteries 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/cells co-localized with HCHWA-D arterial A beta. Focal HLA-DR/CD11c positivity was observed at the media/adventitia junction of AD/HCHWA-D arteries in the absence of local A beta, but not in controls. Monocyte/macrophage marker positivity co-localizing with radial A beta appeared continuous with perivascular cells and microglia clustering perivascularly. These results suggest that (a) MPS cells are topographically associated with HCHWA-D arterial A beta and radial arteriolar A beta, and (b) HLA-DR/CD11c immunoreactivity may appear at the media/adventitia junction prior to A beta. The latter finding and the assumed formation of radial A beta at the media/adventitia junction may relate to involvement of the abluminal basement membrane in CAA pathogenesis. The role of MPS cells in this process remains to be established.
authors.affiliation: Department of Neurology, Leiden University Hospital, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Maat-Schieman
authors.forename: S G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: A J
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: J
authors.initials: J
authors.lastname: Haan
authors.forename: R A
authors.initials: RA
authors.lastname: Roos
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor