BDNF Genetic Variations Increase the Risk of Alzheimer's Disease-Related Depression

Article type: Research Article

Authors: Borroni, Barbara^{a; *} | Grassi, Mario^b | Archetti, Silvana^c | Costanzi, Chiara^a | Bianchi, Marta^a | Caimi, Luigi^b | Caltagirone, Carlo^d | Di Luca, Monica^e | Padovani, Alessandro^a

Affiliations: [a] Center for Aging Brain and Dementia, Department of Neurology, University of Brescia, Italy | [b] Department of Health Sciences, Section of Medical Statistics & Epidemiology, University of Pavia, Italy | [c] III Laboratory of Biotechnology, University of Bresci, Italy | [d] Department of Neurology, University “Tor Vergata”, Rome and IRCCS Santa Lucia, Rome, Italy | [e] Department of Pharmacological Sciences, University of Milan, Italy

Correspondence: [*] Address for correspondence: Barbara Borroni, M.D., Clinica Neurologica, Università degli Studi di Brescia, Pza Spedali Civili, 1 – 25100 Brescia, Italy. Tel.: +39 303995632; Fax: +39 303995027; E-mail: bborroni@inwind.it.

Note: [] Communicated by Valeria Drago

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.

Keywords: Alzheimer's disease, brain-derived neurotrophic factor (BDNF), depression, genetics, haplotype, polymorphism

DOI: 10.3233/JAD-2009-1191

Journal: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 867-875, 2009