The Effects Of Rs405509 On APOEε4 Non-carriers In Non-demented Aging

Background and Objective:The most well-known susceptibility gene for Alzheimer’s disease(AD)is apolipoprotein E(APOE),and multiple studies have shown that the APOEε4 allele might impair brain structure and function in non-demented people.Other genetic variants,on the other hand,are frequently missed when assessing the neurological impacts of APOE.rs405509 is a newly identified single nucleotide polymorphism(SNP)associated with AD,which is located in the APOE gene promoter region and can regulate APOE gene transcriptional activity.In addition,rs405509T/T pure heterozygotes increased the risk of AD development compared to rs405509T/G and G/G groups.It’s unclear how this APOE gene variation influences human brain aging at this time.This experiment used resting-state fMRI and neuropsychological scales to investigate the effects of rs405509 on the brain during non-demented aging.Methods:According to the genotype of rs405509,blood samples were collected from the individuals,genotyped,and the subjects were separated into two groups: G allele group(T/G+G/G)and T/T pure-hybrid group.Blood oxygen level-dependent functional magnetic resonance(BOLD-fMRI)is a new approach for studying brain cortex activity.The imaging principle is that after neurons are activated,the ratio of oxyhemoglobin to deoxyhemoglobin in the local blood changes,resulting in magnetization.The magnetic resonance equipment detects the rate change.The subjects underwent resting-state functional MRI and high-resolution structural imaging.All participants were evaluated using a GE Signa HDX 3.0 Tesla scanner system with an 8-channel phased-array coil,and they were instructed to keep their heads motionless,be silent,close their eyes,and stay awake for as long as possible.The Auditory Verbal Learning Test(AVLT),Mini-Mental State Examination(MMSE),Symbol Digit Modifying Test(SDMT),and other cognitive ability tests were administered by trained professionals.To investigate the effects of rs405509 on brain function during non-demented aging,functional analysis of local activity intensity and altered functional connectivity in the brain,along with a series of clinical neuropsychological scales to fully assess the effects of the APOE gene on neurological function.Results:There were no significant differences in age,gender,or educational years between rs405509 T/T genotype and G-allele carriers groups.T/T allele carriers had lower MMSE(p < 0.001),AVLT-Delayed Recall(p = 0.014),AVLT-T(p = 0.032),and SDMT(p = 0.025)scores than G-allele carriers,indicating a reduction in overall cognitive status,memory,and attention.T/T allele carriers showed decreased amplitude of low frequency fluctuation(ALFF)in the right middle frontal gyrus,decreased percent amplitude of fluctuation(PerAF)in the right middle frontal gyrus,increased regional homogeneity(ReHo)in the right cerebellar tonsil and decreased ReHo in the right putamen,and decreased degree centrality(DC)in the left middle frontal gyrus after rigorous multiple comparison correction.Additionally,substantial relationships between cognitive function and these neuroimaging changes were discovered(p < 0.05).Conclusion:These findings suggest that the T/T allele may act as an independent risk factor that can influence brain function in different regions in non-demented aging.These preliminary findings show that APOE promoter polymorphisms play a significant role in the brain and shed light on the significance of the rs405509 polymorphism in affecting brain function and influencing the risk of developing Alzheimer’s disease in non-demented aging.The combination of early neuropsychological scales and noninvasive resting-state functional MRI allows for early intervention and prevention in genetically at-risk populations.