No evidence for genetic association or linkage of the cathepsin D (CTSD) exon 2 polymorphism and Alzheimer disease

Lars Bertram, Suzanne Guénette, Jennifer Jones, Devon Keeney, Kristina Mullin, Adam Crystal, Sanjay Basu, Stephen Yhu, Amy Deng, G. William Rebeck, Bradley T. Hyman, Rodney Go, Melvin McInnis, Deborah Blacker, Rudolph Tanzi

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations and did not detect an association between CTSD and AD. The first sample was family-based and induded 436 subjects from 134 sibships discordant for AD that were analyzed using the sibship disequilibrium test (SDT, p = 0.68) and the sib transmission/disequilibrium test (Sib-TDT, p = 0.81). The second sample of 200 AD cases and 182 cognitively normal controls also failed to show significant differences in the allele or genotype distribution in cases versus controls (X2, p = 0.91 and p = 0.88, respectively). In addition, two-point linkage analyses in an enlarged family sample (n = 670) did not show evidence for linkage of the chromosomal region around CTSD. Thus, our analyses on more than 800 subjects suggest that if an association between the CTSD exon 2 polymorphism and AD exists, it is likely to be smaller than previously reported.

Original languageEnglish (US)
Pages (from-to)114-116
Number of pages3
JournalAnnals of neurology
Issue number1
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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