Backgrounds: Down syndrome (DS) is the most common chromosomal abnormality. The most important factor in DS is increased maternal age so after the age of 35, the risk of Down syndrome in pregnancy increases. Down synd...Backgrounds: Down syndrome (DS) is the most common chromosomal abnormality. The most important factor in DS is increased maternal age so after the age of 35, the risk of Down syndrome in pregnancy increases. Down syndrome can be diagnosed during pregnancy by prenatal screening. Nondisjunction in cell divisions is the main cause of the DS. Apo lipoprotein E is a 317 amino acid glycoprotein that plays an essential role in metabolism and cholesterol transport. Alzheimer’s disease (AD) is one of the symptoms of adults with DS. The apoE allele e4 has been identified as a risk factor for AD and also, played a main role in nondisjunction. An increased risk of AD in mothers of adults with DS has been reported. We hypothesized that young mothers of DS children (Methods: In this case-control study, 33 DS children and their parents were compared in case of age with 90 families without any history of DS. Genotyping was performed by ARMS-PCR technique. Statistical analysis was performed by SPSS v.21 software. Results: It indicated that there is a significant difference in allele distribution between case and control groups. The C allele for 112 codon of APOE gene and the C allele for 158 codon of APOE gene may associate with nondisjunction. In 112 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.000006, OR = 2.66, 95% CI = 1.74 - 4.06). In 158 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.0000, OR = 3.89, 95% CI = 2.38 - 6.34). E4 allele frequency in mothers of DS is about 14% more than those in control group. According to results of this study the C allele in 158 codon of APOE gene and the C allele in 112 codon of APOE gene could be considered as susceptibility genetic factors for nondisjunction in Northeast of Iran.展开更多
Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evoluti...Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.展开更多
BACKGROUND： Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer＇s disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampa...BACKGROUND： Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer＇s disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons. OBJECTIVE： To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4 DESIGN, TIME AND SETTING： This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006. MATERIALS： Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5 g were selected for this study. Cholesterol and apolipoprotein E4 （apoE4） were purchased from Sigma Company （USA）, bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312. METHODS： Hippocampal neurons were divided into three groups： a normal control group （routinely added media）, a model group （exposed to media containing 40 mg/L cholesterol and 30 mg/L apoE4 for 24 hours） and a bilobalide B group （exposed to media containing 160 mg/L bilobalide B for 16 hours, and then with addition of 40 mg/L cholesterol and 30 mg/L apoE4 for an additional 24 hours）. MAIN OUTCOME MEASURES： Levels of acetylcholine （ACh） and activity of acetylcholinesterase （ACHE） and choline acetyltransferase （CHAT） in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively. RESULTS： The ACh level was significantly lower in the model group than that in the normal control group （P 〈 0.01）, while it was markedly higher in the bilobalide B group than in the model group （P 〈 0.05）. Activity of AChE was significantly decreased in the model group compared with the normal control group （P 〈 0.05）. However, there was no significant difference between the model group and the bilobalide B group （P 〉 0.05）. Activity of ChAT was significantly lower in the model group than in the normal control group （P 〈 0.01）, while the activity was significantly higher in the bilobalide B group than in the model group （P 〈 0.05）. CONCLUSION： Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting the synthesis, but not the degradation, of ACh.展开更多
Most studies investigating genetics of dementia have focused on Alzheimer’s disease, but little is known about the genetics of vascular dementia (VD). The aim of this study was to identify the association between Apo...Most studies investigating genetics of dementia have focused on Alzheimer’s disease, but little is known about the genetics of vascular dementia (VD). The aim of this study was to identify the association between Apolipoprotein E4 (Apo E4) genotype and VD in cerebrally infarcted patients. The study was conducted on 100 patients with cerebral infarction: 50 had VD (cases) and 50 didn’t have dementia (controls). Diagnosis of VD was based on Mini-Mental State Examination, Cambridge Cognitive Examination (CAMCOG), the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria for the diagnosis of VD (DSM-IV), Hachinski Ischemic Score, and computed tomography of the brain (CT brain). Apo E4 allele was assessed through DNA genotyping. The study showed that hypertension (p = 0.027, OR = 4.71), diabetes mellitus (p = 0.003, OR = 6.05) and Apo E4 allele (p = 0.017, OR = 13.39) were the independent risk factors of VD among studied participants. The study concluded that cerebrally infarcted patients with Apo E4 genotype are at high risk of developing VD.展开更多
目的分析载脂蛋白E(apoE)ε4等位基因分型的健康老年人静息态全脑功能连接强度(FCS)特征,探讨apoEε4基因型调控认知正常老年人的脑功能网络拓扑组织结构的机制。方法入选的44例健康老年人的人口统计学资料、MRI数据、apoEε4信息均来...目的分析载脂蛋白E(apoE)ε4等位基因分型的健康老年人静息态全脑功能连接强度(FCS)特征,探讨apoEε4基因型调控认知正常老年人的脑功能网络拓扑组织结构的机制。方法入选的44例健康老年人的人口统计学资料、MRI数据、apoEε4信息均来自美国公开数据库。根据是否携带apoEε4将入选者分为apoEε4组14例和非apoEε4组30例。进行静息态功能MRI(rs-fMRI)扫描和神经心理学评估,采集rs-fMRI数据进行预处理,计算全脑长程和短程FCS值,比较2组差异。结果静息状态下,与非apoeEε4组比较,apoEε4组右侧岛叶长程FCS值减低(簇大小为183个体素,14656.88±3762.93 vs 20905.82±10245.85,P<0.05),左侧岛叶、右侧岛叶及右侧海马/梭状回短程FCS值减低(簇大小分别为91、232和75个体素,P<0.05)。结论携带apoEε4的健康老年人可不表现认知功能的损害,但其FCS值与非携带者存在差异,这可能是apoEε4基因潜在的神经生物学效应。展开更多
Intracerebral hemorrhage(ICH)is a serious clinical disease with high morbidity,whose pathogenesis might be related to apolipoprotein E(APOE)gene polymorphisms.To comprehensively evaluate the risk factors for ICH occur...Intracerebral hemorrhage(ICH)is a serious clinical disease with high morbidity,whose pathogenesis might be related to apolipoprotein E(APOE)gene polymorphisms.To comprehensively evaluate the risk factors for ICH occurrence,we performed a meta-analysis.We searched online databases to identify eligible studies based on the relationship between APOE genetic polymorphisms and ICH occurrence risk.Specific and pooled odds ratios(ORs)were calculated and by assessing small study bias,we drew the relationship between APOE polymorphisms and ICH risk.We included 15 eligible studies in our study containing a total of 1642 ICH samples and 5545 normal controls.The comparison of e4 andε3 APOE genotypes revealed that specific and pooled ORs showed a significantly increased odds ratio in ICH patients with theε4 genotype,indicating thatε4 gene is a risk factor for ICH occurrence,and the heterogeneity is acceptable.Similarly,it was found that theε2 genotype also contributed to the incidence rate of ICH.However,after the subgroup analysis by ethnicity,this APOE genetic polymorphism acted as a harmful factor only in white populations,but did not show an effect in Asian populations.It was suggested that both 82 andε4 APOE alleles were risk factors for ICH in general.They were risk factors in white populations only,neither had a detectable effect in Asian populations after subgroup analysing by ethnicity.展开更多
In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large North...In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer＇s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype （P = 0.017） and allele （P = 0.007） frequencies of the rs2072064 polymorphism between late-onset Alzheimer＇s disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer＇s disease （odds ratio （OR） = 0.792, 95% confidence interval （CI） = 0.670-0.937, P = 0.007）. When the data were stratified by the apolipoprotein E E4 status, there was a significant difference only among apolipoprotein E E4 non-carriers （genotypic P = 0.001, allelic P = 0.001）. Furthermore, the association between rs2072064 and late-onset Alzheimer＇s disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E E4 carrier status （dominant model： OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model： OR = 0.655, 95% CI = 0.448-0.959, P= 0.030; additive model： OR = 0.792, 95% CI = 0.661-0.950, P = 0.012）. These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer＇s disease in a Northern Han Chinese population from the Qingdao area.展开更多
目的 探讨 Apo E基因多态性与血管性痴呆 ( Va D)的相互关系。方法 应用聚合酶链反应 -限制性片段长度多态性 ( PCR-RFLP)技术 ,检测脑卒中后 Va D组与未发生 Va D的对照组患者的 Apo E基因型分布及出现频率。结果 Apo E基因的ε4 ...目的 探讨 Apo E基因多态性与血管性痴呆 ( Va D)的相互关系。方法 应用聚合酶链反应 -限制性片段长度多态性 ( PCR-RFLP)技术 ,检测脑卒中后 Va D组与未发生 Va D的对照组患者的 Apo E基因型分布及出现频率。结果 Apo E基因的ε4 / 4基因型 ,在 Va D组的出现频率明显高于未发生 Va D的对照组 ( P<0 .0 5 ) ,其余各基因型的出现频率 ,两组间差异无显著性 ( P>0 .0 5 )。结论 Apo E基因的 ε4 / 4基因型与 Va D的发生密切相关 ;等位基因ε4可能是 Va D的一种遗传易感性因子。展开更多
文摘Backgrounds: Down syndrome (DS) is the most common chromosomal abnormality. The most important factor in DS is increased maternal age so after the age of 35, the risk of Down syndrome in pregnancy increases. Down syndrome can be diagnosed during pregnancy by prenatal screening. Nondisjunction in cell divisions is the main cause of the DS. Apo lipoprotein E is a 317 amino acid glycoprotein that plays an essential role in metabolism and cholesterol transport. Alzheimer’s disease (AD) is one of the symptoms of adults with DS. The apoE allele e4 has been identified as a risk factor for AD and also, played a main role in nondisjunction. An increased risk of AD in mothers of adults with DS has been reported. We hypothesized that young mothers of DS children (Methods: In this case-control study, 33 DS children and their parents were compared in case of age with 90 families without any history of DS. Genotyping was performed by ARMS-PCR technique. Statistical analysis was performed by SPSS v.21 software. Results: It indicated that there is a significant difference in allele distribution between case and control groups. The C allele for 112 codon of APOE gene and the C allele for 158 codon of APOE gene may associate with nondisjunction. In 112 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.000006, OR = 2.66, 95% CI = 1.74 - 4.06). In 158 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.0000, OR = 3.89, 95% CI = 2.38 - 6.34). E4 allele frequency in mothers of DS is about 14% more than those in control group. According to results of this study the C allele in 158 codon of APOE gene and the C allele in 112 codon of APOE gene could be considered as susceptibility genetic factors for nondisjunction in Northeast of Iran.
基金supported by the National Natural Science Foundation of China,No.81501106(to CF)Fund of Taishan Scholar Project(to CF)+1 种基金the Natural Science Foundation of Shandong Province,No.ZR2020QH106(to YH)the Medical and Health Science and Technology Development Plan of Shandong Province,No.202203010799(to QS)。
文摘Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.
基金the Natural Science Foundation of Tianjin Educational Bureau, No.20030117
文摘BACKGROUND： Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer＇s disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons. OBJECTIVE： To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4 DESIGN, TIME AND SETTING： This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006. MATERIALS： Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5 g were selected for this study. Cholesterol and apolipoprotein E4 （apoE4） were purchased from Sigma Company （USA）, bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312. METHODS： Hippocampal neurons were divided into three groups： a normal control group （routinely added media）, a model group （exposed to media containing 40 mg/L cholesterol and 30 mg/L apoE4 for 24 hours） and a bilobalide B group （exposed to media containing 160 mg/L bilobalide B for 16 hours, and then with addition of 40 mg/L cholesterol and 30 mg/L apoE4 for an additional 24 hours）. MAIN OUTCOME MEASURES： Levels of acetylcholine （ACh） and activity of acetylcholinesterase （ACHE） and choline acetyltransferase （CHAT） in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively. RESULTS： The ACh level was significantly lower in the model group than that in the normal control group （P 〈 0.01）, while it was markedly higher in the bilobalide B group than in the model group （P 〈 0.05）. Activity of AChE was significantly decreased in the model group compared with the normal control group （P 〈 0.05）. However, there was no significant difference between the model group and the bilobalide B group （P 〉 0.05）. Activity of ChAT was significantly lower in the model group than in the normal control group （P 〈 0.01）, while the activity was significantly higher in the bilobalide B group than in the model group （P 〈 0.05）. CONCLUSION： Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting the synthesis, but not the degradation, of ACh.
文摘Most studies investigating genetics of dementia have focused on Alzheimer’s disease, but little is known about the genetics of vascular dementia (VD). The aim of this study was to identify the association between Apolipoprotein E4 (Apo E4) genotype and VD in cerebrally infarcted patients. The study was conducted on 100 patients with cerebral infarction: 50 had VD (cases) and 50 didn’t have dementia (controls). Diagnosis of VD was based on Mini-Mental State Examination, Cambridge Cognitive Examination (CAMCOG), the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria for the diagnosis of VD (DSM-IV), Hachinski Ischemic Score, and computed tomography of the brain (CT brain). Apo E4 allele was assessed through DNA genotyping. The study showed that hypertension (p = 0.027, OR = 4.71), diabetes mellitus (p = 0.003, OR = 6.05) and Apo E4 allele (p = 0.017, OR = 13.39) were the independent risk factors of VD among studied participants. The study concluded that cerebrally infarcted patients with Apo E4 genotype are at high risk of developing VD.
文摘目的分析载脂蛋白E(apoE)ε4等位基因分型的健康老年人静息态全脑功能连接强度(FCS)特征,探讨apoEε4基因型调控认知正常老年人的脑功能网络拓扑组织结构的机制。方法入选的44例健康老年人的人口统计学资料、MRI数据、apoEε4信息均来自美国公开数据库。根据是否携带apoEε4将入选者分为apoEε4组14例和非apoEε4组30例。进行静息态功能MRI(rs-fMRI)扫描和神经心理学评估,采集rs-fMRI数据进行预处理,计算全脑长程和短程FCS值,比较2组差异。结果静息状态下,与非apoeEε4组比较,apoEε4组右侧岛叶长程FCS值减低(簇大小为183个体素,14656.88±3762.93 vs 20905.82±10245.85,P<0.05),左侧岛叶、右侧岛叶及右侧海马/梭状回短程FCS值减低(簇大小分别为91、232和75个体素,P<0.05)。结论携带apoEε4的健康老年人可不表现认知功能的损害,但其FCS值与非携带者存在差异,这可能是apoEε4基因潜在的神经生物学效应。
基金the National Natural Science Foundation of China(No.81471201 and No.81171089).
文摘Intracerebral hemorrhage(ICH)is a serious clinical disease with high morbidity,whose pathogenesis might be related to apolipoprotein E(APOE)gene polymorphisms.To comprehensively evaluate the risk factors for ICH occurrence,we performed a meta-analysis.We searched online databases to identify eligible studies based on the relationship between APOE genetic polymorphisms and ICH occurrence risk.Specific and pooled odds ratios(ORs)were calculated and by assessing small study bias,we drew the relationship between APOE polymorphisms and ICH risk.We included 15 eligible studies in our study containing a total of 1642 ICH samples and 5545 normal controls.The comparison of e4 andε3 APOE genotypes revealed that specific and pooled ORs showed a significantly increased odds ratio in ICH patients with theε4 genotype,indicating thatε4 gene is a risk factor for ICH occurrence,and the heterogeneity is acceptable.Similarly,it was found that theε2 genotype also contributed to the incidence rate of ICH.However,after the subgroup analysis by ethnicity,this APOE genetic polymorphism acted as a harmful factor only in white populations,but did not show an effect in Asian populations.It was suggested that both 82 andε4 APOE alleles were risk factors for ICH in general.They were risk factors in white populations only,neither had a detectable effect in Asian populations after subgroup analysing by ethnicity.
文摘In a recent genome-wide association study, the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer＇s disease in Caucasians. Here, we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer＇s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao, China. Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype （P = 0.017） and allele （P = 0.007） frequencies of the rs2072064 polymorphism between late-onset Alzheimer＇s disease patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer＇s disease （odds ratio （OR） = 0.792, 95% confidence interval （CI） = 0.670-0.937, P = 0.007）. When the data were stratified by the apolipoprotein E E4 status, there was a significant difference only among apolipoprotein E E4 non-carriers （genotypic P = 0.001, allelic P = 0.001）. Furthermore, the association between rs2072064 and late-onset Alzheimer＇s disease remained significant by logistic regression analysis after adjustment for age, gender, and the apolipoprotein E E4 carrier status （dominant model： OR = 0.787, 95% CI = 0.619-1.000, P = 0.050; recessive model： OR = 0.655, 95% CI = 0.448-0.959, P= 0.030; additive model： OR = 0.792, 95% CI = 0.661-0.950, P = 0.012）. These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer＇s disease in a Northern Han Chinese population from the Qingdao area.
文摘目的 探讨 Apo E基因多态性与血管性痴呆 ( Va D)的相互关系。方法 应用聚合酶链反应 -限制性片段长度多态性 ( PCR-RFLP)技术 ,检测脑卒中后 Va D组与未发生 Va D的对照组患者的 Apo E基因型分布及出现频率。结果 Apo E基因的ε4 / 4基因型 ,在 Va D组的出现频率明显高于未发生 Va D的对照组 ( P<0 .0 5 ) ,其余各基因型的出现频率 ,两组间差异无显著性 ( P>0 .0 5 )。结论 Apo E基因的 ε4 / 4基因型与 Va D的发生密切相关 ;等位基因ε4可能是 Va D的一种遗传易感性因子。
