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American Journal of Pathology, Vol 142, 1449-1457, Copyright © 1993 by American Society for Investigative Pathology

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Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease

AJ Rozemuller, RA Roos, GT Bots, W Kamphorst, P Eikelenboom and WE Van Nostrand
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.

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.

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