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Anatomic, Metabolic, Neuropsychological, and Molecular Genetic Studies of Three Pairs of Identical Twins Discordant for Dementia of the Alzheimer's Type
Anand Kumar, MD;
Mark B. Schapiro, MD;
Cheryl L. Grady, PhD;
Martha F. Matocha, PhD;
James V. Haxby, PhD;
Angela M. Moore, MS;
Jay S. Luxenberg, MD;
Peter H. St George-Hyslop, PhD;
Charles D. Robinette, PhD;
Melvyn J. Ball, MD;
Stanley I. Rapoport, MD
Arch Neurol. 1991;48(2):160-168.
Abstract
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• Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.
Author Affiliations
From the Laboratory of Neurosciences, National Institute on Aging of the National Institutes of Health, Bethesda, Md (Drs Kumar, Schapiro, Grady, Matocha, Haxby, Luxenberg, and Rapoport and Mr Moore); Department of Neurology and Program in Neurosciences, Harvard Medical School, Boston, Mass (Dr St George-Hyslop); National Academy of Sciences, National Research Council, Washington, DC (Dr Robinette); and the Departments of Pathology, Clinical Neurological Sciences, and Psychiatry, University of Western Ontario, London (Dr Ball).
Footnotes
Accepted for publication August 2, 1990.
Reprint requests to Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bldg 10, Room 6C103, Bethesda, MD 20892 (Dr Rapoport).
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