Absence of the 40-kDa form of (2'-5')oligoadenylate synthetase and its corresponding mRNA from skin fibroblasts derived from Alzheimer disease patients.

Abstract

Cultured skin fibroblasts derived from Alzheimer disease patients fail to express the 1.6-kilobase (kb) mRNA and the corresponding 40-kDa form of (2'-5')oligoadenylate (2-5A) synthetase when exposed to interferon. In addition, the 3.6-kb mRNA, which is present in normal fibroblasts, is barely detectable in the Alzheimer disease counterpart. The deficiency of the 2-5A synthetase 1.6-kb mRNA and its corresponding protein is not related to an impairment of interferon receptors but most probably represents an alteration in the expression of the 2-5A synthetase gene. The data have potential implications for the diagnosis of Alzheimer disease and demonstrate that the absence of a specific form of 2-5A synthetase is linked to a disease state.