Hereditary Central Nervous System γ-Trace Amyloid Angiopathy and Stroke in Icelandic Families

Abstract

Hereditary central nervous system amyloid angiopathy occurring in Icelanders is the first human disease known to be caused by selective deposition of fragments of the alkaline microprotein γ-trace forming amyloid fibrils in the walls of the brain and spinal cord arteries. This causes single or multiple strokes ending fatally in most cases. A regulation of cysteine proteinase activity has been suggested as the function of γ -trace. Studies of 128 affected members in eight families from the same geographical area, indicate transmission of an autosomal dominant gene over two centuries. About 90% of those who died of this disorder were less than 50 years. The studies indicate, that in few members the carrier state is compatible with reaching old age. This CNS angiopathy is characterized by an abnormally low value of γ-trace in the CSF or one third of the mean value found in comparable normal adults. Estimation of γ-trace in the CSF is presently the only test available for supporting diagnosis of the disorder and differentiating it from other types of cerebral hemorrhage. This test will significantly improve genetic counseling and make search for genetic linkage possible.