Association between Nerve Growth Factor Gene Polymorphism and Executive Dysfunction in Japanese Patients with Early-Stage Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Abstract

Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.

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

“…Our results may help to elucidate the functional roles of not only the NT-3 gene, but also other neurotrophin gene polymorphisms described in previous studies [17,18,23,24]. Furthermore, elucidating the detailed associations between NT-3 gene diversity and behaviors in patients with AD will be an important task in the future.…”

“…Moreover, NT-3 protects cortical neurons against A-β dependent neural cell death by limiting caspase-8, caspase-9 and caspase-3 cleavage [16]. While some previous studies have reported neurotrophin polymorphisms as a risk factor for AD in Japanese populations, our group reported that representative single-nucleotide polymorphisms (SNPs) of NGF and BDNF influenced executive function during limited demented stages, as assessed using the frontal assessment battery (FAB) [17][18][19][20][21].…”

“…The method used for the NT-3 SNP (rs6332, rs6489630) genotyping, a SNaPshot analysis (Applied Biosystem), has been described in previous reports [17,18,31]. If the genotype of the SNPs was unclear or ambiguous using the SNaPshot method, we rechecked and confirmed the genotype using PCR products and direct nucleotide sequencing with an ABI 3730 DNA analyzer (sequencing reactions were performed using BigDye Terminator v3.1 Cycle Sequencing Kits; Applied Biosystems).…”

Association between BDNF Polymorphism (Val66Met) and Executive Function in Patients with Amnestic Mild Cognitive Impairment or Mild Alzheimer Disease

“…A recent study showed that Val66Met determines the differences in the age-related effects on hippocampal volume and cognitive function between valine homozygosity (Val/Val) and methionine (Met) carriers [16][17][18]. Moreover, we found that a nerve growth factor polymorphism (rs6330) influences the executive function of mild-stage AD and A-MCI patients in a recent study [19]. These results imply that the effects of neurotrophin gene polymorphisms on cognitive function may be altered during the aging process or according to the stage of neurodegeneration.…”

Frontal Assessment Battery as a Useful Tool to Differentiate Mild Cognitive Impairment due to Subcortical Ischemic Vascular Disease from Alzheimer Disease

“…It has been widely applied in studies on various target groups [17,18,19,20,21]. Researchers have discovered that neural substrates related to performances on the FAB include both cortical and subcortical areas, such as the middle frontal gyrus, inferior frontal, insula [22], callosomarginal, and precentral regions [23].…”