title: Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease.
abstract: Brain amyloidosis with abundant beta/A4 protein deposition in plaques and cortical and meningeal vessels is found in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). In contrast to AD, no neuritic pathology or classical congophilic plaques are found in HCHWA-D. Unlike most AD cases, the congophilic angiopathy in HCHWA-D is very severe. It is still unknown whether beta/A4 deposits in plaques and vessels have the same origin. In this study, we have used frozen cortical tissue of HCHWA-D and AD patients to investigate the beta/A4 amyloid protein and the amyloid precursor protein (APP) in different types of plaques and congophilic angiopathy. Immunohistochemical staining was conducted using antibodies against synthetic beta/A4 proteins and antibodies against APP including MAbP2-1, a monoclonal antibody against purified protease nexin-2, which is the secreted form of APP. In contrast to immunohistochemical studies on formalin-fixed, paraffin-embedded tissue, frozen tissue of HCHWA-D patients revealed a very high number of beta/A4 plaques resembling AD. All plaques were of the diffuse type. Double-staining with MabP2-1 and beta/A4 antisera revealed: 1) the presence of APP immunoreactivity in classical plaques and transitional forms; 2) the absence of APP immunoreactivity in diffuse plaques in HCHWA-D and AD; and 3) pronounced APP immunoreactivity in congophilic vessels in HCHWA-D in contrast to weak APP staining in congophilic vessels in AD. Together these findings suggest that: a) the presence of APP in plaques is related to neuritic changes; b) different processes occur in amyloid formation in plaques and vessels; and c) differences exist between the process of amyloid formation in HCHWA-D and AD.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: R A
authors.initials: RA
authors.lastname: Roos
authors.forename: G T
authors.initials: GT
authors.lastname: Bots
authors.forename: W
authors.initials: W
authors.lastname: Kamphorst
authors.forename: P
authors.initials: P
authors.lastname: Eikelenboom
authors.forename: W E
authors.initials: WE
authors.lastname: Van Nostrand
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000686:Amyloidosis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003224:Congo Red; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000648:ultrastructure; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003224:Congo Red