Association between Neurotrophin-3 Polymorphisms and Executive Function in Japanese Patients with Amnestic Mild Cognitive Impairment and Mild Alzheimer Disease

Abstract

Background: We investigated whether neurotrophin (NT)-3 polymorphisms influenced the executive function of patients with 2 separate disease stages with similar dementia conditions: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD). Methods: Among 215 outpatients with dementia and MCI, 155 with mild AD (n = 108) or A-MCI (n = 47) were recruited and divided into three genotypic groups based on the representative NT-3 functional polymorphisms rs6332 and rs6489630. Next, we compared the frontal assessment battery (FAB) total and subtest scores between the three genotypic groups. Results: The total FAB score was not significantly associated with the rs6332 and rs6489630 genotypes; however, the conflicting instructions score among the 6 subtests was significantly associated with the rs6332 genotype (p < 0.05). Moreover, in patients with mild AD, the conflicting instructions score differed significantly among the three genotypic groups of rs6332 (p < 0.05) (G/G < A/A: p = 0.042 and G/A < A/A: p = 0.041). No significant differences in any other demographic variables were observed among the three genotypes of rs6332 and rs6489630. Conclusion: These results suggested that an NT-3 polymorphism, rs6332, may significantly influence executive function, reflecting interference performances among patients with mild-stage AD.

Applications of blood-based protein biomarker strategies in the study of psychiatric disorders

“…In contrast, the neurotrophin 3 growth factor has been found to be increased during episodes of depression in bipolar disorder patients (Fernandes et al, 2010). This protein controls survival and differentiation of neurons (Fan et al, 2010) and has also been associated with executive function (Kobayashi et al, 2012).…”

Genetic Association between Neurotrophin-3 Polymorphisms and Alzheimer's Disease in Japanese Patients

“…We found that the executive function of G allele carriers was significantly lower than that of A allele carriers among AD patients. However, carrying the A allele was associated with a risk of EAD in the present study [20]. The functional roles of rs6332 might influence executive dysfunction in comparatively older AD patients (approx.…”

“…The method used to identify the NTF-3 SNP (rs6332, rs6489630, rs4930767) genotypes, a SNaPshot analysis (Applied Biosystems, Foster City, Calif., USA), has been described in previous reports [20,21,32]. If the genotype of the SNP was unclear or ambiguous when determined using the SNaPshot method, we rechecked and confirmed the genotype using PCR products and direct nucleotide sequencing using an ABI 3730 DNA Analyzer [sequencing reactions were performed using BigDye Terminator v3.1 Cycle Sequencing Kits (Applied Biosystems)].…”

“…While some previous studies had reported BDNF polymorphisms to be risk factors for AD in Japanese populations, we observed that some single nucleotide polymorphisms (SNPs) of neurotrophins are associated with cognitive impairment in patients with AD [20,21,22,23,24,25]. Among the candidate genes in the neurotrophin family, Kunugi et al [23] found that a missense mutation (Gly/-63/Glu) in the NTF-3 gene was associated with a risk of AD; however, its mutant type (-63 Glu) was too rare in Caucasian populations to be investigated in subsequent studies in other countries [23,26].…”

“…selective attentional tasks and performance execution) [28,29]. A silent polymorphism, rs6332, is located within Pro- NTF-3 gene exon 1 and influences the executive function in patients with limited mild-stage AD, but not mild cognitive impairment (MCI) [20]. The rs4930767 polymorphism in the promoter region of the same gene does not appear to be associated with any measure of ADHD [29].…”