A new promoter polymorphism in the alpha-1-antichymotrypsin gene is a disease modifier of Alzheimer's disease

Federico Licastro, Martina Chiappelli, Luigi M E Grimaldi, Kevin Morgan, Noor Kalsheker, Elena Calabrese, Alistair Ritchie, Elisa Porcellini, Giuliana Salani, Massimo Franceschi, Nicola Canal

Research output: Contribution to journalArticlepeer-review

Abstract

Increased levels of alpha-1-antichymotrypsin (ACT), a protease inhibitor and an acute phase protein, have been found in the brain and peripheral blood of patients with Alzheimer's disease (AD). Patients from northern Italy with a clinical diagnosis of probable AD, and patients with early onset AD (EOAD) from UK with AD neuropathological diagnosis were genotyped for a new polymorphism in the promoter region of the ACT gene which has been shown to affect ACT expression. A subset of patients with clinical AD from northern Italy was also followed up for 2 years and monitored for cognitive decline. The ACT TT promoter genotype was associated with an increased risk of EOAD independently from the presence of the apolipoprotein E (APOE) ε 4 allele. After manifestation of the disease the ACT TT genotype was also associated with faster cognitive decline in patients with the APOE allele ε 4. The ACT gene appears to influence the early clinical development of the disease, and the interaction of the ACT and APOE genes affects clinical progression of AD.

Original languageEnglish
Pages (from-to)449-453
Number of pages5
JournalNeurobiology of Aging
Volume26
Issue number4
DOIs
Publication statusPublished - Apr 2005

Keywords

  • Alpha-1-antichymotrypsin gene
  • Alzheimer's disease risk
  • APOE ε alleles
  • Cognitive decline
  • Promoter polymorphism

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

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