Amyloid B protein precursor gene and hereditary cerebral hemorrhage with amyloidosis

• Published in: Science (American Association for the Advancement of Science) 1990-06, Vol.248 (4959), p.1120
• Main Authors: Van Broeckhoven, C, Haan, J, Bakker, E, Hardy, J.A, Van Hul, W, Wehnert, A, Vegter-Van der Vlis, M, Roos, R.A.C
• Format: Article
• Language: English
• Subjects: Amyloidosis; Physiological aspects
• ISSN: 0036-8075; 1095-9203

Cerebral amyloid angiopathy (CAA) is a hereditary condition involving recurrent, often fatal, cerebral hemorrhages (extensive bleeding within the brain). One form of this disorder has been detected in four Dutch families, and is called human hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). Alzheimer's disease (AD) and Down syndrome share several features with HCHWA-D, suggesting that this hereditary disease might be a subtype of AD with vascular involvement, and that the pathogenesis of the two conditions may be related. The shared features include deposition of amyloid B protein (ABP) in the walls of blood vessels and in the thin membranes covering the brain, as well as the accumulation of ABP in senile plaques (round, abnormal structures in the brain). Experiments were performed to see whether the genetic defect associated with HCHWA-D is related to the gene for amyloid precursor protein (APP), the protein from which ABP is made. This gene has been implicated in AD. Twenty patients from two Dutch families contributed samples of DNA (genetic material). Results showed that the mutation that appears to cause HCHWA-D occurs in the APP gene. These findings suggest that a mutation of a single base in the coding sequence of APP is responsible for the defect in HCHWA-D. (Consumer Summary produced by Reliance Medical Information, Inc.)