Role of BDNF Val66Met functional polymorphism in Alzheimer's disease-related depression

Borroni, B.; Archetti, S.; Costanzi, C.; Grassi, M.; Ferrari, M.; Radeghieri, A.; Caimi, L.; Caltagirone, C.; Di Luca, M.; Padovani, A.; for the ITINAD Working Group,

doi:10.1016/j.neurobiolaging.2007.11.023

« Previous Next »Neurobiology of Aging
Volume 30, Issue 9 , Pages 1406-1412, September 2009

Role of BDNF Val66Met functional polymorphism in Alzheimer's disease-related depression

B. Borroni
- Center for Aging Brain and Dementia, Department of Neurology, University of Brescia, Italy
- Corresponding author at: Clinica Neurologica, Università degli Studi di Brescia, Pza Spedali Civili, 1-25100 Brescia, Italy. Tel.: +39 0303995632; fax: +39 0303995027.
S. Archetti
- III Laboratory of Biotechnology, University of Brescia, Italy
C. Costanzi
- Center for Aging Brain and Dementia, Department of Neurology, University of Brescia, Italy
M. Grassi
- Department of Health Sciences, Section of Medical Statistics & Epidemiology, University of Pavia, Italy
M. Ferrari
- III Laboratory of Biotechnology, University of Brescia, Italy
A. Radeghieri
- III Laboratory of Biotechnology, University of Brescia, Italy
L. Caimi
- III Laboratory of Biotechnology, University of Brescia, Italy
C. Caltagirone
- Department of Neurology, University “Tor Vergata”, Rome and IRCCS Santa Lucia, Rome, Italy
M. Di Luca
- Department of Pharmacological Sciences, University of Milan, Italy
A. Padovani
- Center for Aging Brain and Dementia, Department of Neurology, University of Brescia, Italy
for the ITINAD Working Group

Received 23 July 2007; received in revised form 22 October 2007; accepted 24 November 2007. published online 07 January 2008.

Abstract

Background

The gene encoding brain-derived neurotrophic factor (BDNF) has been suggested as a candidate for major depression, and for depression susceptibility in different neurological and psychiatric diseases. No study has investigated the role of BDNF genetic variation and depressive symptoms in Alzheimer's disease (AD).

Objective

The aim of this study was to assess the genetic contribution of BDNF Val66Met functional polymorphism to AD-related depression.

Methods

Two-hundred and sixty-four AD patients underwent clinical and neuropsychological examination as well as an evaluation of behavioral and psychiatric disturbances. They were subsequently divided into two subgroups according to the presence (AD-D) or the absence (AD-nD), based on DSM-IV criteria for depression in AD. In each subject, BDNF Val66Met functional polymorphism and apolipoprotein E (APOE) genotype were evaluated.

Results

In our sample, 35.2% of patients (n=93) reported AD-related depressive symptoms. Compared to patients bearing no polymorphisms (BDNF G/G), BDNF G/A carriers showed more than twofold-time risk (OR=2.38; 95%CI=1.38–4.13), and BDNF A/A carriers had a threefold-time risk (OR=3.04; 95%CI=1.15–8.00) for depression in AD.

Accordingly, considering the allele frequencies, BDNF A allele was significantly over-represented in AD-D (32.8%) compared to AD-nD (19.0%) (OR=2.08; 95%CI=1.38–3.13). An association between the number of carried A allele and the severity of depressive symptoms was observed (P<0.002). No effect of APOE genotype on risk for depression was found.

Conclusions

The present findings provide evidence of BDNF genetic variation role in the susceptibility to AD-related depression. This study puts emphasis on the usefulness of considering genetic background for better defining individualized risk profiles in AD.

Keywords: Alzheimer's disease, Depression, Brain-derived neurotrophic factor (BDNF), Polymorphism