BDNF genetic variations increase the risk of Alzheimer's disease-related depression

Barbara Borroni, Mario Grassi, Silvana Archetti, Chiara Costanzi, Marta Bianchi, Luigi Caimi, Carlo Caltagirone, Monica Di Luca, Alessandro Padovani

Research output: Contribution to journalArticle

Abstract

The gene encoding the brain-derived neurotrophic factor (BDNF) has been demonstrated as a candidate for Alzheimer's disease-related depression (AD-D) susceptibility. Additionally, an association between AD-D and the functional valine to methionine (Val66Met) polymorphism has been reported. The aim of this study was to assess the genetic contribution of other BDNF variants to AD-D. Two-hundred forty-five AD patients were divided into two subgroups according to the presence (AD-D) or the absence (AD-nD) of depressive symptoms. Four single-nucleotide polymorphisms within BDNF gene were considered, i.e., C270T, rs2049045 C/G, G196A (Val66Met), and G11757C. In our sample, 35.5% of patients (n = 87) reported AD-related depressive symptoms. The individual SNP analysis showed an association between G196A and G11757C genotypes and AD-D. Accordingly, considering the allele frequencies, BDNF 196*A allele was significantly overrepresented in AD-D compared to AD-nD (OR = 1.80, 95% CI = 1.19-2.72), as well as BDNF 11757*C allele (OR = 1.90, 95% CI = 1.25-2.90). Haplotype analyses revealed that the alleles at four loci (C270T, rs2049045 C/G, G196A, G11757C) interacted to further increase the risk of AD-D. Compared to the most common not-at-risk C-C-G-G haplotype, C-G-A-C (OR = 3.55, 95% CI = 1.44-8.76, P = 0.006) and C-C-A-C haplotypes (OR = 1.72, 95% CI = 1.03-2.87, P = 0.037) were overrepresented in AD-D. This study suggests that BDNF genetic variations play a role in the susceptibility to AD-related depression.

Original languageEnglish
Pages (from-to)867-875
Number of pages9
JournalJournal of Alzheimer's Disease
Volume18
Issue number4
DOIs
Publication statusPublished - 2009

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Keywords

  • Alzheimer's disease
  • Brain-derived neurotrophic factor (BDNF)
  • Depression
  • Genetics
  • Haplotype
  • Polymorphism

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Borroni, B., Grassi, M., Archetti, S., Costanzi, C., Bianchi, M., Caimi, L., Caltagirone, C., Di Luca, M., & Padovani, A. (2009). BDNF genetic variations increase the risk of Alzheimer's disease-related depression. Journal of Alzheimer's Disease, 18(4), 867-875. https://doi.org/10.3233/JAD-2009-1191