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PEN2 is not a genetic risk factor for Alzheimer’s disease in a large family sample

From the Genetics and Aging Research Unit (Drs. Bertram and Tanzi, R. Menon, K. Mullin, M. Parkinson, and M.L. Bradley), Center for Aging, Genetics, and Neurodegeneration, Department of Neurology, and Gerontology Research Unit (Dr. Blacker), Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, and Department of Epidemiology (Dr. Blacker), Harvard School of Public Health, Boston, MA.

Address correspondence and reprint requests to Dr. R.E. Tanzi, Genetics and Aging Research Unit, Center for Aging, Genetics, and Neurodegeneration, CNY 114, 16 St., Charlestown, MA 02129; e-mail: tanzi{at}helix.mgh.harvard.edu

PEN2 is a reasonable Alzheimer’s disease (AD) candidate gene because it is a necessary component of the -secretase complex that generates ß-amyloid peptide. Moreover, its gene (PEN2) maps to a highly significant linkage region on chromosome 19q13. Four common polymorphisms in PEN2 were tested for genetic association with AD in a large and carefully ascertained AD family sample (789 subjects from 202 nuclear families) using single-locus and haplotype-based analyses. These results do not suggest PEN2 to be a major AD risk factor.

Received July 1, 2003. Accepted in final form September 17, 2003.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the January 27 issue to find the title link for this article.