Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders

Vitamin E (alpha-tocopherol) is an essential nutrient and an important anti oxidant. Its plasma levels are dependent upon oral intake, absorption and t ransfer of the vitamin to a circulating lipoprotein. The latter step is con trolled by alpha-tocopherol transfer protein (alpha-TTP), which is a 278 am ino acid protein encoded on chromosome 8, known to be synthesized in the li ver. Mutations in alpha-TTP are associated with a neurological syndrome of spinocerebellar ataxia, called ataxia with vitamin E deficiency (AVED). Ear lier studies suggested that alpha-TTP is found only in the liver. In order to establish whether alpha-TTP is expressed in the human brain, and what re lationship this has to AVED, we studied immunohistochemically the presence of alpha-TTP in the brains of a patient with AVED, normal subjects, and pat ients with Alzheimer's disease (AD), Down's syndrome (DS), cholestatic live r disease (CLD) and abetalipoproteinemia (ABL). The neuropathology of both AD and DS is thought to be related in part to oxidative stress. The disease s of AVED, of cholestatic liver disease, and of abetalipoproteinemia are th ought to be due to lack of circulating tocopherol, leading to inadequate pr otection against oxidative damage. We demonstrate the presence of alpha-TTP in cerebellar Purkinje cells in patients having vitamin E deficiency state s or diseases associated with oxidative stress. (C) 1999 Elsevier Science B .V. All rights reserved.