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New genetic risk factor for susceptibility to Alzheimer's disease

Molecular Psychiatry

Alzheimer's disease (AD) researchers at the University of Pittsburgh have singled out a new genetic risk factor for the debilitating brain disease that affects 4 million Americans today and will strike as many as 14 million during the next 50 years.

In a decade-long research study following more than 300 first-degree relatives of 189 Alzheimer's patients, the researchers identified a small area of chromosome 10 that, when combined with the previously identified APOE E4 gene, significantly increase a person's risk of developing the disease. This combination of genes produced a 16-fold increase in the risk of AD among first-degree relatives. By comparison, this effect is greater than the increased risk of lung cancer caused by smoking. These new results are supported by independent studies of AD patients and controls from Pittsburgh, Boston, and Bonn, Germany.

Dr. Zubenko and his colleagues studied normal individuals between the ages of 40 and 75 who were first-degree relatives of patients with AD. The subjects were given standard memory evaluation tests to be certain they had not suffered any cognitive decline prior to the start of the study, and then blood samples were drawn to identify genetic and biochemical risk factors for AD and related disorders. Eighteen people developed AD after 11.5 years of regular follow-up evaluations. Ongoing assessments of the remainder of the group and the continuing search for new risk factors are in progress.

These findings may provide new molecular targets for therapeutic drug development and will help researchers design trials involving subjects who have the greatest likelihood of responding to therapy and for whom successful therapy would have the greatest impact. Furthermore, the newly discovered risk locus affects brain levels of dopamine, the neurotransmitter used by neurons that degenerate in Parkinson's disease. As a result, the new findings may have relevance for both of these common neurodegenerative disorders.


Citation source: Molecular Psychiatry 2001 Volume 6, number 4, pages 413-419.

For further information on this work, please contact Dr. George S. Zubenko, WPIC, E 1230, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. Office phone: 412-624-5186; e-mail:

Molecular Psychiatry is published by the Nature Publishing Group.

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ARTICLE: "D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals"

AUTHORS: GS Zubenko, HB Hughes III, JS Stiffer

Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 and Department of Biological Sciences, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, PA 15213

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