Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease

Elena Mariani, Davide Seripa, Tiziana Ingegni, Giuseppe Nocentini, Francesca Mangialasche, Sara Ercolani, Antonio Cherubini, Antonio Metastasio, Alberto Pilotto, Umberto Senin, Patrizia Mecocci

Research output: Contribution to journalArticlepeer-review


The proteins cathepsin D, encoded by CTSD gene, and α2-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of β-amyloid. In these proteins two amino acid polymorphisms (CTSD-Ala/Val C→T and A2M-Ile/Val A→G) have been associated with an increased risk for Alzheimer's disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD-C/T and A2M-A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD-T allele and the CTSD-C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD-T subjects is 1.93 [95% confidence interval (CI) = 1.01-3.72], and 2.07 (95% CI = 1.01-4.21) after adjustment for age, sex and APOE ε4+ status, while no significant association was found for the A2M-A/G polymorphism. The coexistence of the CTSD-T with the A2M-G allele synergistically increased the OR for AD to 2.69 (95% CI = 1.13-6.34) [2.82 (95% CI = 1.12-7.17) after adjustment], and to 3.29 (95% CI = 1.33-8.16) if estimated for the allelic combination. Our data suggest that the CTSD-T allele of the CTSD-C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD-T with the A2M-G allele seems to increase this risk.

Original languageEnglish
Pages (from-to)187-191
Number of pages5
JournalJournal of the Neurological Sciences
Issue number2
Publication statusPublished - Sep 25 2006


  • α-Macroglobulin
  • Alzheimer's disease
  • Cathepsin D
  • Interaction
  • Polymorphisms

ASJC Scopus subject areas

  • Ageing
  • Clinical Neurology
  • Surgery
  • Neuroscience(all)
  • Developmental Neuroscience
  • Neurology


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