Increased oxysterols associated with iron accumulation in the brains and visceral organs of acaeruloplasminaemia patients

Acaeruloplasminaemia is characterized by excessive neurovisceral iron accum ulation due to mutation of the caeruloplasmin gene. Excess iron functions a s a potent catalyst of biological oxidation, and increased iron concentrati on is associated with the products of lipid peroxidation in the serum and c erebrospinal fluid. We investigated whether the amount of iron accumulated paralleled lipid peroxidation levels in acaeruloplasminaemia tissues, exami ning brains and visceral organs of two affected patients at autopsy for iro n and copper content, and oxysterols, including 7-hydroxycholesterol and 7- ketocholesterol, which are directly produced from cholesterol by active oxy gen species. The amount of iron accumulated in various tissues was correlat ed with the levels of the oxysterols. These findings suggest that lipid per oxidation produced by the intracellular accumulation of iron is involved in the pathogenesis of acaeruloplasminaemia.