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Neurobiol Aging. 2009 Sep;30(9):1406-12. doi: 10.1016/j.neurobiolaging.2007.11.023. Epub 2008 Jan 7.

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

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  • 1Center for Aging Brain and Dementia, Department of Neurology, University of Brescia, Italy.



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).


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


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.


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.


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.

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