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Current Status and Future Prospects

Deborah Blacker, MD, ScD; Rudolph E. Tanzi, PhD

Arch Neurol. 1998;55:294-296.

Four genes involved in the development of Alzheimer disease have been identified. Three fully penetrant (deterministic) genes lead to the development of Alzheimer disease in patients younger than 60 years: the amyloid -protein precursor on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1. Together, they account for about half of this early-onset form of the disease. One genetic risk factor—apolipoprotein E-4—is associated with late-onset Alzheimer disease. It accounts for a substantial fraction of disease burden but seems to act primarily to lower the age of disease onset. In general, none of these genes can be easily adapted for use as a diagnostic or predictive test for Alzheimer disease. Research activity includes searching for additional genes, especially for late-onset disease, and elucidating the mechanism of action of all identified genes as part of a long-term effort to develop more effective therapeutic and preventive strategies.

From the Gerontology Research Unit, Department of Psychiatry (Dr Blacker), and the Genetics and Aging Unit, Department of Neurology (Dr Tanzi), Massachusetts General Hospital and Harvard Medical School; and the Department of Epidemiology, Harvard School of Public Health (Dr Blacker), Boston, Mass.

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