DISTRIBUTION OF BETA A4 PROTEIN AND AMYLOID PRECURSOR PROTEIN IN HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS DUTCH TYPE AND ALZHEIMERS-DISEASE/

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 (HCHW A-D). In contrast to AD, no neuritic pathology or classical congophili c 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 stud y, we have used frozen cortical tissue of HCHWA-D and AD patients to i nvestigate the beta/A4 amyloid protein and the amyloid precursor prote in (APP) in different types of plaques and congophilic angiopathy. Imm unohistochemical staining was conducted using antibodies against synth etic beta/A4 proteins and antibodies against APP including MAbP2-1, a monoclonal antibody against purified protease nexin-2, which is the se creted form of APP. In contrast to immunohistochemical studies on form alin-fixed, paraffin-embedded tissue frozen tissue of HCHWA-D patients revealed a very high number of beta/A4 plaques resembling AD. AU plaq ues were of the diffuse type. Double staining with MAbP2-1 and beta/A4 antisera revealed 1) the presence of APP immunoreactivity in classica l plaques and transitional forms, 2) the absence of APP immunoreactivi ty in diffuse plaques in HCHWA-D and AD; and 3) pronounced APP immunor eactivity in congophilic vessels in HCHWA-D in contrast to weak APP st aining in congophilic vessels in AD. Together these findings suggest t hat a) the presence of APP in plaques is related to neuritic changes, b) different processes occur in amyloid formation in plaques and vesse ls; and c) differences exist between the process of amyloid formation in HCHWA-D and AD.