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Xenobiotic metabolism in Alzheimer's disease

Departments of Neurology (Drs. Heafield, Sturman, and Williams) and Biochemistry (Drs. Steventon and Waring), University of Birmingham, Birmingham, UK.

Using 5 methods, we assessed the ability of patients with a clinical diagnosis of Alzheimer's disease (AD) to handle xenobiotics. Patients with AD, compared with controls, have reduced sulfoxidation of the probe drug S-carboxymethyl-l-cysteine; they also form less of the sulfate conjugate of acetaminophen. In addition, they have lower activity of the enzyme thiolmethyltransferase. In contrast, the capacity to oxidize debrisoquin and to acetylate sulfamethazine was normal. These findings suggest that a major risk factor for the development of AD is a skewed capacity for xenobiotic metabolism especially of compounds containing sulfur.

Address correspondence and reprint requests to Dr. Rosemary H. Waring, The University of Birmingham, School of Biochemistry, PO Box 363, Birmingham B15 2TT, UK.

Received October 6, 1989. Accepted for publication in final form December 18, 1989.

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