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Science 1 June 1990:
Vol. 248. no. 4959, pp. 1120 - 1122
DOI: 10.1126/science.1971458
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Articles

Science, Vol 248, Issue 4959, 1120-1122
Copyright © 1990 by American Association for the Advancement of Science

articles

Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch)

C Van Broeckhoven, J Haan, E Bakker, JA Hardy, W Van Hul, A Wehnert, M Vegter-Van der Vlis, and RA Roos

Born Bunge Foundation, Department of Biochemistry, University of Antwerp, Belgium.

Human hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), an autosomal dominant form of cerebral amyloid angiopathy (CAA), is characterized by extensive amyloid deposition in the small leptomeningeal arteries and cortical arterioles, which lead to an early death of those afflicted in their fifth or sixth decade. Immunohistochemical and biochemical studies have indicated that the amyloid subunit in HCHWA-D is antigenically related to and homologous in sequence with the amyloid beta protein isolated from brains of patients with Alzheimer's disease and Down syndrome. The amyloid beta protein is encoded by the amyloid beta protein precursor (APP) gene located on chromosome 21. Restriction fragment length polymorphisms detected by the APP gene were used to examine whether this gene is a candidate for the genetic defect in HCHWA-D. The data indicate that the APP gene is tightly linked to HCHWA-D and therefore, in contrast to familial Alzheimer's disease, cannot be excluded as the site of mutation in HCHWA-D.


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