Variations in the <i>BDNF</i> Gene in Autopsy-Confirmed Alzheimer’s Disease and Dementia with Lewy Bodies in Japan

Abstract

Background/Aim: Brain-derived neurotrophic factor (BDNF) is associated with the hippocampus and the nigrostriatal dopaminergic function. Data showing that its level was reduced in Alzheimer’s disease (AD) and Parkinson’s disease (PD) suggested that the BDNF function must play an important role in the pathogenetics of these diseases. Indeed, variation in the BDNF gene may confer susceptibility to AD and PD development. Recently, a functional BDNF Val66Met polymorphism has been found to be associated with episodic memory and hippocampal function, with intracellular trafficking, and with activity-dependent secretion of BDNF. To date, there have been several conflicting reports on the correlation between AD or PD and Val66Met or C270T polymorphism in the BDNF promoter region, although no data on this relationship have been published with respect to dementia with Lewy bodies (DLB). In the present study, we investigated a possible association between such BDNF polymorphisms and susceptibility to AD or DLB. Methods:BDNF genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method in autopsy-confirmed human samples. Results and Conclusion: On comparing patients and controls, the distribution of BDNF genotypes and alleles did not differ significantly. Our findings suggest that it is unlikely that these BDNF polymorphisms play a major role in the pathogenesis of AD and DLB in the Japanese population.

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

“…Previous studies have reported five positive results (12-16) and 21 negative results (19,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) between the BDNF Val66Met polymorphism and AD. In the present meta-analysis, no significant association was found between BDNF Val66Met and AD (P>0.05, Table II).…”

“…Heterozygous carriers of the T-allele tend to have a higher risk of developing AD than non-carriers (36). There have been a total of four significant results (13,(17)(18)(19)) and 14 non-significant results (28)(29)(30)(31)(34)(35)(36)(37)40,41,(43)(44)(45) among the previous association studies between the BDNF C270T polymorphism and AD. In the present meta-analysis, the BDNF C270T polymorphism was found to increase the risk of AD by 88% in Asians under the dominant model.…”

“…For BDNF Val66Met, there have been five positive results in Europeans (12)(13)(14)(15) and Asians (16), and 21 negative results (among 18 studies) in Europeans (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), Asians (19,(38)(39)(40)(41)(42) and Africans (29). For BDNF C270T, there have been four positive results in Europeans (13,17) and Asians (18,19) and 14 negative results in Europeans (28)(29)(30)(31)(34)(35)(36)(37)(43)(44)(45), Asians (40,41) and Africans (29). For BCHE-K variants, there have been six positive results in Europeans (46-51) and 22 negative results in Europeans (5,(52)(53)(54)(55)…”

Alzheimer disease and neuroplasticity: New approaches and new targets in pharmacotherapy

“…Polymorphism of the BDNF has been implicated with higher risk for AD. Especially for non-ApoE4 carriers and specific ethnic groups, this effect is well documented (100,101). A very interesting link is the fact that during aging and in AD, tau pathology starts in the entorhinal cortex and proceeds along the retrograde transport pathways of BDNF to the subiculum and CA1 subfield and then to the basal forebrain, amygdale and finally to several cortical regions (90).…”

Association of Brain-Derived Neurotrophic Factor (BDNF) Gene Snps G196A and C270T with Alzheimer’s Disease: A Meta-Analysis

“…Detailed characteristics of all eligible studies included in meta-analysis are reported in Table 1. One overall study was conducted on BDNF 196GA polymorphism and 3 ethnicity specific studies were conducted, that includes 8 studies on American populations [30][31][32][33][34][35][36], 11 studies on Asian populations [37][38][39][40][41][42][43][44][45][46][47] and 12 studies on European populations [35,[48][49][50][51][52][53][54][55][56][57][58]. Moreover, one overall study was also conducted on BDNF 270CT polymorphism and 3 ethnicity specific studies were also possible, that includes 5 studies on American populations [30,31,33,34,59], 7 studies on Asian populations [37,39,41,42,44,46,60] and 7 studies on European populations [48,49,52,…”