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Science 22 December 2000:
Vol. 290. no. 5500, pp. 2302 - 2303
DOI: 10.1126/science.290.5500.2302
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Reports

Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10q

Lars Bertram,1 Deborah Blacker,23 Kristina Mullin,1 Devon Keeney,1 Jennifer Jones,1 Sanjay Basu,1 Stephen Yhu,1 Melvin G. McInnis,4 Rodney C. P. Go,5 Konstantinos Vekrellis,6 Dennis J. Selkoe,6 Aleister J. Saunders,1 Rudolph E. Tanzi1*

Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Abeta , the principal component of beta -amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the IDE gene, in 435 multiplex AD families. These analyses revealed significant evidence of linkage for adjacent markers (D10S1671, D10S583, D10S1710, and D10S566), which was most pronounced in late-onset families. Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the IDE gene.

1 Genetics and Aging Unit, Department of Neurology,
2 Gerontology Research Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
3 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
4 Department of Psychiatry, Johns Hopkins University Medical Institutions, Baltimore, MD 21287, USA.
5 Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL 35294, USA.
6 Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
*   To whom correspondence should be addressed at Genetics and Aging Unit, Massachusetts General Hospital-East, 149 13th Street, Charlestown, MA 02129, USA. E-mail: tanzi{at}helix.mgh.harvard.edu

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