Apolipoprotein A-I-derived amyloid in atherosclerotic plaques of the humanaorta

Previous studies have shown that the amyloid localized to the aortic intima may be a biochemical entity different from other forms of localized amyloi d, The amyloid fibril protein in one patient studied consisted of an N-term inal fragment of apolipoprotein A-1 (apo A-1). Since this patient was later shown to carry a missense mutation in the apo A-1 gene, leading to a delet ion at position 107 of the mature protein, the question remained whether wi ld-type apo A-1 is amyloidogenic. In autopsy specimens from the thoracic ao rta from 69 individuals, intimal atherosclerotic plaque-related amyloid was present in 11 cases (16%) and amyloid outside plaques in 37 cases (54%), T he immunoreactivity of amyloid localized to the aortic intima was evaluated with the aid of antisera against N-terminal segments of apo A-1, The amylo id in association with atherosclerotic plaques was positively labelled by i mmunohistochemistry. The amyloid fibril protein from one patient, previousl y shown not to carry any mutation in the apo A-1 gene, was purified and sho wn by amino acid sequence analysis to be of apo A-1 nature. The result show s that wild-type apo A-1 is amyloidogenic and gives rise to a common locali zed form of amyloid associated with atherosclerosis, Copyright (C) 2000 Joh n Wiley & Sons, Ltd.