Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment

Forlenza, Orestes Vicente; Diniz, Breno S.; Teixeira, Antônio Lúcio; Ojopi, Elida P.B.; Talib, Leda Leme; Mendonça, Vanessa Amaral; Izzo, Giselle; Gattaz, Wagner F.

doi:10.3109/15622971003797241

Cited by 118 publications

(92 citation statements)

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“…This may explain the impaired memory and perceptual speed performance observed in the met-BDNF carriers of this aging cohort. Our findings are supported by a previous study showing that the presence of the met-BDNF allele may predict a worse cognitive outcome in patients with MCI (Forlenza et al 2010) and cognitive impairment in Parkinson patients (Guerini et al 2009). …”

Section: Discussionsupporting

confidence: 81%

“…Research also implicates the met-BDNF allele in working (short-term) memory impairments in bipolar patients (Rybakowski et al 2003(Rybakowski et al , 2006. Recently, it was suggested that the presence of the met-BDNF allele, particularly in association with apolipoprotein E (APOE*E4), may predict a worse cognitive outcome in patients with mild cognitive impairment (MCI; Forlenza et al 2010) and may negatively impact on cognitive function in Parkinson's disease (Guerini et al 2009). In contrast, however, studies on patients with other diseases suggest that the met allele in the rs6265 SNP may play a protective role against the decline of processing speed function.…”

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confidence: 99%

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Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

Laing

Mitchell

Wersching³

et al. 2011

AGE

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Cognitive aging processes are underpinned by multiple processes including genetic factors. The brain-derived neurotrophic factor (BDNF) has been suggested to be involved in age-related cognitive decline in otherwise healthy individuals. The genderspecific role of the BDNF gene in cognitive aging remains unclear. The identification of genetic biomarkers might be a useful approach to identify individuals at risk of cognitive decline during healthy aging processes. The aim of this study was to investigate the associations between three singlenucleotide polymorphisms (SNPs) in the BDNF gene and domains of cognitive functioning in normal cognitive aging. The sample, comprising 369 participants (M=72.7 years, SD=4.45 years), completed an extensive neuropsychological test battery measuring memory, motor function, and perceptual speed. The relationships between the SNPs rs6265, rs7103411, and rs7124442 and cognitive domains were examined. While significant main effects of BDNF SNPs on cognitive function were found for the association between rs7103411 and memory performance, gender-specific analyses revealed for females significant main effects of rs7103411 for memory and of rs6265 for perceptual speed independent of the APOE*E4 status and education. The finding for the association between rs6265 and perceptual speed in females remained significant after Bonferroni correction for multiple comparisons. None of the analyses showed significant results for males. This study is the first to implicate that the SNPs rs6265 and rs7103411 affect cognitive function in the elderly in a genderspecific way.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

Laing

Mitchell

Wersching³

et al. 2011

AGE

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“…The current observation that BDNF Met 66 in preclinical ADAD was associated with increased tau, hippocampal dysfunction and memory impairment is consistent with the role that CNS BDNF plays in synaptic excitation, long-term potentiation and neuronal plasticity (Hariri et al, 2003;Peng et al, 2005;Garzon and Fahnestock, 2007;Forlenza et al, 2010;Fahnestock, 2011;Lee et al, 2012;Lu et al, 2013). Evidence of a mechanistic relationship between BDNF and tau has been shown in cellular studies that demonstrate that BDNF can induce rapid dephosphorylation of tau through TrkB activation (Elliott et al, 2005) and that BDNF loss in Alzheimer's disease is specific to tangle-bearing neurons (Ferrer et al, 1999).…”

Section: Discussionsupporting

confidence: 53%

“…Clinical studies of the role of BDNF in Alzheimer's disease are limited by the absence of validated biomarkers for CNS BDNF (Forlenza et al, 2010;Kim et al, 2015). However, the BDNF Val66Met (rs6265) polymorphism Met protein can result in reduced dendritic trafficking and synaptic localization of the protein and up to a 30% reduction in activity-dependent BDNF secretion Chen et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

BDNFVal66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease

Lim

Hassenstab

Cruchaga

et al. 2016

Brain

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) for a scientific commentary on this article. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-b-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-b in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) "4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation noncarriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val 66 homozygotes, 48 Met 66 carriers). Among preclinical mutation carriers, Met 66 carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val 66 homozygotes. Cortical amyloid-b and cerebrospinal fluid amyloidb 42 levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val 66 homozygotes and Met 66 carriers. There was an effect of APOE on amyloid-b levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-b on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met 66 carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-b in autosomal dominant Alzheimer's disease.

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“…This is in agreement with Angelucci et al [26] and Forlenza et al [27] who reported that serum BDNF concentration is considered as a key player in the activitydependent synaptic plasticity that is involved in the learning and memory processes.…”

Section: El-alameey and Ahmedsupporting

confidence: 81%

Serum Brain Derived Neurotrophic Factor as Biomarker for Epilepsy Diagnosis in Egyptian Children With Epilepsy; Relationship to Disease Severity and Cognitive Function.

El-Alameey

Ahmed

2018

Asian J Pharm Clin Res

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Objectives: This study was designed to estimate serum brain-derived neurotrophic factor (BDNF) concentration in a group of Egyptian children with epilepsy to clarify its utility as a biomarker for epilepsy diagnosis and to evaluate its relationship with their cognitive function and disease severity. Methods:Intelligence was assessed using Arabic version of the WISC-R test. Serum concentration of BDNF was assessed using enzyme-linked immunosorbent assay in 40 children with epilepsy and 40 apparently healthy children of matched age and sex controls.Results: Of total 40 epileptic patients aged 6-12 years, the mean age was 8.32 ± 0.7 years and male to female ratio was 1.5:1. The mean serum BDNF concentration and cognitive IQ scores were statistically significantly reduced in the studied patient's group versus to controls (p<0.001). There were highly significant differences in serum BDNF concentration as regards epileptic severity. Serum concentration of BDNF showed significantly positive correlation with cognitive, verbal, performance, and totals IQ scores and negative correlation with the age at the onset of seizures, and duration of therapy. The linear regression analysis showed a statistically significant association between age at the onset of seizures, duration of therapy, cognitive function, and serum BDNF concentrations among the studied patients. Conclusions:Concentration of BDNF in serum is involved in the mechanism of epileptogenesis in children with epilepsy. It should be used as a helpful marker for epilepsy diagnosis and detection of severity.

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Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment

Cited by 118 publications

References 30 publications

Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

BDNFVal66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease

Serum Brain Derived Neurotrophic Factor as Biomarker for Epilepsy Diagnosis in Egyptian Children With Epilepsy; Relationship to Disease Severity and Cognitive Function.

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