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

Article Abstract:

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.)

Physiological aspects

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Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type

Article Abstract:

A rare inherited disease, hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), is characterized by recurrent cerebral hemorrhage (bleeding in the brain). This condition leads to death in the fifth or sixth decade of life. Certain changes in the brains of these patients resemble changes associated with Alzheimer's disease (AD), a progressive condition resulting in a total cognitive loss, and with Down syndrome. These similarities led researchers to investigate whether the same gene that has been implicated in AD could also be affected in HCHWA-D. The gene is responsible for manufacturing amyloid B protein, which is a component of abnormal deposits found in the brains of victims of both conditions. Four families have been identified with the hemorrhagic disorder, and DNA (genetic material) from two family members was analyzed. Results showed that a mutation appeared at one position of the gene that codes for ABP, leading to an alteration in the structure of that protein (glutamine appears instead of glutamic acid) in these patients. This abnormality may be the reason that the altered protein becomes deposited in blood vessel walls. (Consumer Summary produced by Reliance Medical Information, Inc.)

Genetic aspects

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