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

Borroni, Barbara; Archetti, Silvana; Costanzi, Chiara; Grassi, Mario; Ferrari, Maria Tereza Martins; Radeghieri, Annalisa; Caimi, Luigi; Caltagirone, Carlo; Luca, Monica Di; Padovani, Alessandro

doi:10.1016/j.neurobiolaging.2007.11.023

Cited by 65 publications

(39 citation statements)

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“…12 Various studies have shown a relationship between the polymorphism type and the severity of clinical and imaging features in healthy subjects and in different neuropsychiatric and neurologic disorders. 12,[21][22][23][24][25][26][27][28] Because of the suspected role of BDNF in RTT pathogenesis, the dramatic wide-scale effect of BDNF in the CNS in general, the relative disadvantage of the p.V66M variant in culture, and clinical studies in other diseases, we decided to investigate the relationship between the presence of this BDNF variant and RTT clinical severity. In order to overcome the variability of severity between mutations, we also examined separately those patients with the two most common mutations, p.T158 M and p.R168X.…”

mentioning

confidence: 99%

The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome

Zeev

Bebbington²,

Ho³

et al. 2009

Neurology

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mentioning

confidence: 99%

The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome

Zeev

Bebbington²,

Ho³

et al. 2009

Neurology

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“…Older participants are also more likely to suffer from late-onset depression, which has been suggested to often precede the onset of demen-tia, especially Alzheimer's disease (Saczynski et al 2010;Dal Forno et al 2005), which is also associated with a more pronounced hippocampal degeneration (Laakso et al 1998;Ryu et al 2010). BDNF Val66Met polymorphism has been previously associated with depressive symptoms in patients with Alzheimer's disease (Borroni et al 2009). In our sensitivity analyses, however, we found no association between depression and MMSE score, nor did entering the MMSE score in the multivariate model change the association between the BDNF polymorphisms and depression.…”

Section: Discussionmentioning

confidence: 99%

“…Older participants are also more likely to suffer from late-onset depression, which often precedes the onset of dementia, especially Alzheimer's disease (Saczynski et al 2010;Dal Forno et al 2005). Alzheimer's disease is also associated with substantial hippocampal degeneration (Laakso et al 1998;Ryu et al 2010), and BDNF polymorphisms (rs6265 and rs7124442) have also been examined in relation to it (Borroni et al 2009;Huang et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

Czira

Wersching

Baune

et al. 2011

AGE

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A large number of studies have examined associations between brain-derived neurotrophic factor (BDNF) gene polymorphisms and depressive symptoms. However, results still remain controversial. Recent studies suggested a significant age and gender effect on the heritability of depression. The potential neurobiological pathways that could possibly mediate this relationship have not been examined so far. Since BDNF is involved in the regulation of neurotransmitter production, a mediating role of neurotransmitters seems plausible. The present study aims to examine the association between three common BDNF singlenucleotid polymorphisms (SNPs; rs7103411, rs7124442, and rs6265) and depressive symptoms in a community-based elderly population taking into account the serum levels of four neurotransmitters, serotonin, dopamine, adrenalin, and noradrenalin, as potential mediating factors. We also examined whether age and gender had a modifying effect on this association. We collected and analyzed the genetic and laboratory data as well as Center for Epidemiologic Studies-Depression scores of 350 community-dwelling elderly individuals (aged 65+ years). We found that the BDNF rs6265 polymorphism was related to the severity of depressive symptoms, and that this association was independent of neurotransmitter levels. Stratified analyses showed that this association was restricted to older individuals (≥74 years) and men. The associations of SNPs rs7103411 or rs7124442 SNP with depressive symptoms were not statistically significant. This study importantly adds to the existing literature by affirming previous assumptions on an age and gender difference in the relation between BDNF genotype and depression. We moreover first-time report a missing mediating role of neurotransmitters in this association.

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“…neuronal atrophy and synapse loss in aged rats and nonhuman primates (137). What is more, a human genetic polymorphism in the gene encoding BDNF has been linked to abnormal brain structure, hippocampal activity and memory in humans (138)(139)(140) and to several psychiatric disorders (141)(142)(143)(144)(145). On a similar note, a polymorphism in the XBP1 promoter has been linked to a risk of AD (146).…”

Section: Potential Mediators Of Xbp1 Signaling In Neuronsmentioning

confidence: 99%

The Transcription Factor XBP1 in Memory and Cognition: implications in Alzheimer’s Disease

Cissé

Duplan

Checler

2016

Mol Med

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X-box binding protein 1 (XBP1) is a unique basic region leucine zipper transcription factor that was isolated two decades ago in a search for regulators of major histocompatibility complex class II gene expression. XBP1 is a very complex protein that regulates many physiological functions, including the immune system, inflammatory responses and lipid metabolism. Evidence over the past few years suggests that XBP1 also plays an important role in pathological settings, since its activity as a transcription factor has profound effects on the prognosis and progression of diseases such as cancer, neurodegeneration and diabetes. Here we provide an overview of recent advances in our understanding of this multifaceted molecule, particularly in regulating synaptic plasticity and memory function, and the implications in neurodegenerative diseases, with an emphasis on Alzheimer's disease.

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

Cited by 65 publications

References 36 publications

The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome

The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

The Transcription Factor XBP1 in Memory and Cognition: implications in Alzheimer’s Disease

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