We tested if the ε4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study.
Among ε4/ε4 individuals, AD risk</span> increased substantially in a dose-dependent manner with the number of <i>APOE</i> promoter SNP rs405509 <i>T</i> alleles in EastAs <i>(TT</i>: OR (odds ratio) = 27.02, <i>p</i> = 8.80 × 10<sup>-94</sup>; <i>GT</i>: OR = 15.87, <i>p</i> = 2.62 × 10<sup>-9</sup>) and EuroAs (<i>TT</i>: OR = 18.13, <i>p</i> = 2.69 × 10<sup>-108</sup>; <i>GT</i>: OR = 12.63, <i>p</i> = 3.44 × 10<sup>-64</sup>), and rs405509-<i>T</i> homozygotes had a younger onset and more severe cortical atrophy than those with <i>G</i>-allele.
In the presented study, we investigated the association between -491 A/T (rs449647), -427C/T, (rs769446) and -219 T/G (rs405509) single nucleotide polymorphisms (SNPs) of APOE gene and AD risk in the Polish population.
These results demonstrate that the rs405509 T/T allele of APOE causes an age-related cognitive decline in non-demented elderly people, possibly by modulating brain network communication efficiency, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.
Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease.
Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 as the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease (AD).
The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer's disease (AD).
Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.
This association is biologically plausible as SNP rs405509 was shown to modify protein binding and transcriptional activity of the APOE protein in vitro and is in linkage disequilibrium with key known variants defining the e2, e3, and e4 alleles that modify risk of atherosclerosis, Alzheimer's disease risk, and progression to AIDS.
The single nucleotide polymorphisms (SNPs) rs449647, rs769446 and rs405509 in the promoter region of the APOE gene have been variously suggested to be epsilon 4-independent risk factors for Alzheimer's disease (AD).
Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.
There was no interaction between rs9331896 in CLU and rs429358 (defining the ɛ4 allele) in APOE in predicting Alzheimer's disease or all dementia (P = 0.39 and P = 0.21).
APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease.