Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta

The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Ferroptosis mechanism and Alzheimer's disease

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.

载脂蛋白E联合临床相关指标预测阿尔兹海默病模型的建立与验证

目的 以载脂蛋白E(ApoE)为基础,结合阿尔茨海默病发病危险因素及临床常见指标,构建阿尔兹海默病发病风险的临床预测模型。方法 从南京市中医院大数据平台中,检索时间为2019年1月至2021年1月两年时间内,阿尔兹海默病患者61例,模糊匹配健康体检者111例。利用LASSO回归筛选危险因素,构建logistic回归预测模型,10折交叉进行区分度验证,bootstrap法进行校准度验证,临床决策曲线评判预测模型的临床指导性,最后以列线图可视化呈现临床预测模型。结果 筛选出12个变量,最终纳入4个危险因素:年龄、游离三碘甲状腺素(FT3)、性别、ApoE。全样本ROC曲线下面积为0.879,10折交叉9次验证后ROC曲线下平均面积为0.864;采用Bootstrap法抽样及Hosmer-Lemeshow校准度检验,结果χ^(2)=6.496,P=0.592>0.05。临床决策曲线阈值概率区间为1%~88.6%。结论 利用年龄、游离三碘甲状腺素、性别、 ApoE构建的临床预测模型对患者进行个体化评估,可以预警阿尔兹海默病,开展早期预防干预,减缓该病的发生发展。

APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer's disease

Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.

APOLIPOPROTEIN E GENE POLYMORPHISMS AND RISK FOR CORONARY ARTERY DISEASE IN CHINESE XINJIANGUYGUR AND HAN POPULATION

Objective To examine the relationship between apolipoprotein E (Apo E) gene polymorphism and risk of coronary artery disease (CAD), analyzing association of polymorphism with classical risk factors. Methods A total of 124 patients (including 84 Han population and 40 Uygur population) with angiographically verified CAD or myocardial infarction were prospectively evaluated. Data referring to hypertension, diabetes, and tobacco consump-tion were recorded. The levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, Apo A1 and B, and triglycerides (TG) were determined. DNA was obtained from 124 patients and 70 controls. In order to determine Apo E genotypes, DNA was PCR amplified and digested with HhaI. The genetic polymorphism of Apo E is due to three common alleles, epsilon(ε) 2, ε3, ε4, at a single autosomal gene locus. These alleles determine the six phenotypes E2/2, E3/3, E4/4, E4/2, E4/3, and E3/2. Results In Uygur population, the frequency of the ε2, ε3, and ε4 was 0.155, 0.648, and 0.197 respectively. In Han po-pulation, the frequency of the ε2, ε3, and ε4 was 0.081, 0.772, and 0.146 respectively. In the patient group, the frequency of the ε2, ε3, and ε4was 0.060, 0.758, and 0.182 respectively. In the control group, the frequency of the ε2, ε3, and ε4 was 0.193, 0.671, and 0.136 respectively. ε2 frequency of Uygur’ patients and controls was 0.050 and 0.290 respectively. Serum low density lipoprotein (LDL) cholesterol, TC, and TG values tended to decrease from the Apo E-4 phenotypes to Apo E-2 phenotypes. When deletion polymorphism of ε2 was compared with the common risk factors for CAD, its risk ratio (RR) is 4.38. Conclusions These studies confirm and find that Apo E phenotype distribution in Uygur population differs significantly from that in Han population in Xinjiang. CAD patients have significantly lower ε2 allele and slightly higher ε3 or ε4 allele frequency than controls, especially in Uygur population. It shows protective effects of ε2 on CAD.

Apolipoprotein E polymorphism in northern Chinese elderly patients with coronary artery disease

Background and objective Apolipoprotein E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. We investigated the relationship between apo E gene polymorphism and the occurrence of coronary artery disease(CAD) in the older population of northern China. Methods The distribution of the HhaI polymorphisms of the apolipoprotein E gene was determined among 55 patients with CAD (CAD group), which was compared with that of 36 elderly subjects without CAD(control group). Results Genotype distributions at both sites (apo E gene 112-bp and 158-bp sites ) were different between the CAD and control groups. The CAD group had lower apolipoprotein E'ε2'frequencies than the control group (P＜0.05). Conclusion Individuals with apolipoprotein E'ε2'are likely to have a reduced risk of developing coronary artery disease as demonstrated by elderly subjects in Northern China.

Apolipoprotein E gene polymorphism in cerebrovascular diseases of the Chinese Naxi populations from Yunnan province

Currently it is not well known whether apolipoprotein E （ApoE） is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases （58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage）, and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.

EFFECTS OF DIPSACUS ASPER AND VITAMIN E ON THE SS NEURONS IN THE HIPPOCAMPAL FORMATION OF RAT MODELS OF ALZHEIMER'S DISEASE

Objective To study the effects of Dipsacus Asper and Vitamin E on the SS neurons in the hippocampal formation of rat models of Alzheimer’s Disease (AD). Methods Established rat models of AD by giving water containing AlCl 3, then treating them with Dipsacus Asper and Vitamin E(VE) for three months, observed the changing condition of rats’ memory through behavior tests, and studied changes of SS neurons in hippocampal formation with immunohistochemical ABC method. Results 3 months after treatment, behavior tests showed that rats’ memory was improved and the SS neurons in each region of hippocampal formation were increased, In CA1,CA2,CA3 and dentate gyrus, there were significant differences among treated groups and control group( P <0.05). In addition to the differences of quantity, the shape of SS neurons changed too: cytoplasm was stained strongly and equally, bodies and processes were rather clear.Conclusion Dipsacus Asper and Vitamin E can restore the SS neurons in AD models and SS neurons in hippocampal formation are related to AD’s cause and development.

Association between apolipoprotein E promoter-219G/T polymorphism and total cholesterol level in patients with Alzheimer disease

BACKGROUND: Many researches have suggested that apolipoprotein E (APOE) and total cholesterol metabolism are closely related with dementia. In the supposed theory, 219 site of APOE promoter region is near gene coding region, so its polymorphism may result in the abnormality of APOE gene and protein expression, and finally lead to dementia. OBJECTIVE: To observe the association between APOE promoter-219G/T polymorphisms with serum total cholesterol in patients with Alzheimer disease, and compare it with non-dementia people. DESIGN: Case-control, comparative observation. SETTING: Department of Neurology, Fengtian Hospital of Shenyang Medical College. PARTICIPANTS: Fifty-five dementia patients including 27 males and 28 females aged (66±3) years and treated in the Department of Neurology, Fengtian Hospital were selected from January 2002 to December 2005 as the Alzheimer disease group. They all diagnosed according to the DSM-Ⅳdiagnostic criteria of Alzheimer disease instituted by American Psychiatry Association in 1994. Meanwhile, 44 none-dementia patients including 21 males and 23 females aged (66±3) years were selected from other clinical departments of Fengtian Hospital as control group. All the participants were informed the detection and agreed. METHODS: Genomic DNA was extracted from the peripheral blood of all subjects, then 'NEST'PCR, DNA sequence and enzyme digestion were adopted to detect the expression of APOE promoter-219 polymorphism, following by biomedical statistics analysis based on the clinical total cholesterol level. MAIN OUTCOME MEASURES: Polymorphism of APOE promoter-219 G/T and total cholesterol level. RESULTS: All 55 dementia patients and 44 non-dementia ones were involved in the result analysis. ①Allele and genotype frequency: The T allele frequency of the Alzheimer disease group was significantly higher than that in the control group [88.2% (97/110), 54.5% (48/88)], while G allele frequency was remarkably lower than that in the control group [11.8%(13/110), 45.5%(40/88), χ2=8.2, P < 0.01]. The TT allele frequency of the Alzheimer disease group was significantly higher than that in the control group [76% (42/55), 48% (21/44)], while GT+GG allele frequency was remarkably lower than that in the control group [24%(13/55), 52%(23/44), χ2=8.7, P < 0.01]. ②Total cholesterol level: The level of the TT genotype patients in the Alzheimer group was obviously higher than that in GT+GG genotype patients (t =2.46, P < 0.05); the cholesterol level in the two genotypes of the control group was similar (P > 0.05). CONCLUSION: TT genotype and allele T in the APOE promoter-219 polymorphisms are the sensitive gene, and genotype TT has a relationship with the increase of total cholesterol level.

Isoform-and cell-state-specific APOE homeostasis and function

Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.

APOE多态性在炎症因子诱导的神经毒性反应性星形胶质细胞中的差异作用

目的:探讨载脂蛋白E(APOE)基因多态性在神经毒性反应性星形胶质细胞中的差异作用,为阿尔茨海默病(AD)发病机制的研究提供理论依据。方法:体外分离培养APOE基因敲除小鼠(APOE^(-/-))原代皮层星形胶质细胞,免疫荧光染色法鉴定细胞纯度。构建人APOE3和APOE4重组过表达质粒,分别转染至原代APOE^(-/-)星形胶质细胞中,以APOE^(-/-)原代细胞为对照,采用Western blotting法检测细胞中APOE和神经胶质酸性蛋白(GFAP)蛋白表达水平,采用酶联免疫吸附试验(ELISA)法检测细胞培养上清中APOE水平。采用白细胞介素1α(IL-1α)、肿瘤坏死因子(TNF)和补体C1q联合刺激转染APOE3和转染APOE4的原代星形胶质细胞制备炎症模型,分为APOE3+PBS组、APOE4+PBS组、APOE3+IL-1α+TNF+CC1q组和APOE4+IL-1α+TNF+C1q组,采用细胞免疫荧光染色法观察各组细胞形态表现,采用实时荧光定量PCR(RT-qPCR)法检测各组细胞中磷脂酰肌醇蛋白聚糖4(Gpc4)、磷脂酰肌醇蛋白聚糖6(Gpc6)、血小板反应蛋白1(Thbs1)、血小板反应蛋白2(Thbs2)、酸性分泌蛋白类似蛋白1(Sparcl1)、胶质细胞源性神经营养因子(GDNF)、C3和S100钙结合蛋白B(S100B)mRNA表达水平,微球吞噬实验检测各组细胞吞噬能力,Western blotting法检测各组细胞中B细胞淋巴瘤2(Bcl-2)和含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)蛋白表达水平。结果:与APOE^(-/-)组比较,转染APOE3和APOE4组细胞中APOE和GFAP蛋白表达水平及细胞培养上清中APOE水平明显升高(P<0.01)。荧光显微镜下观察,分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组星形胶质细胞突起变短,胞体变大;与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组星形胶质细胞突起更短。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞中Gpc4、Gpc6、Thbs1、Thbs2和Sparcl1 mRNA表达水平明显降低(P<0.01);与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞中Gpc4、Gpc6、Thbs1、Thbs2和Sparcl1 mRNA表达水平明显降低(P<0.05或P<0.01)。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞中GDNF mRNA表达水平明显降低(P<0.01),C3和S100B mRNA表达水平明显升高(P<0.01);与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞中GDNFmRNA表达水平明显降低(P<0.05),C3和S100B mRNA表达水平明显升高(P<0.05)。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞吞噬微珠数量明显减少;与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞吞噬微珠数量明显减少。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞中Bcl-2蛋白表达水平明显降低(P<0.05或P<0.01),Caspase-3蛋白表达水平明显升高(P<0.01);与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞中Bcl-2蛋白表达水平明显降低(P<0.01),Caspase-3蛋白表达水平明显升高(P<0.05)。结论:APOE4基因型比APOE3诱导炎症因子能力更强,可诱导神经毒性反应性星形胶质细胞表型,增加神经毒性,影响星形胶质细胞凋亡,从而加剧神经元损伤。

Apolipoprotein E variants correlate with the clinical presentation of paediatric inflammatory bowel disease:A cross-sectional study

BACKGROUND It has been suggested that apolipoprotein E(APOE)polymorphisms are associated with the risk of developing inflammatory bowel disease(IBD)and the early age of disease onset.However,there are no reports regarding the relationship with clinical characteristics and disease severity.AIM To summarise that APOE polymorphisms are associated with the risk of developing IBD and the early age of disease onset.METHODS In total,406 patients aged 3-18 with IBD(192 had ulcerative colitis and 214 had Crohn’s disease)were genotyped using the TaqMan hydrolysis probe assay.Clinical expression was described at diagnosis and the worst flare by disease activity scales,albumin and C-reactive protein levels,localisation and behaviour(Paris classification).Systemic steroid intake with the total number of courses,immunosuppressive,biological,and surgical treatment with the time and age of the first intervention were determined.The total number of exacerbation-caused hospitalisations,the number of days spent in hospital due to exacerbation,the number of relapses,and severe relapses were also estimated.RESULTS Ulcerative colitis patients with the APOEε4 allele had lower C-reactive protein values at diagnosis(P=0.0435)and the worst flare(P=0.0013)compared to patients with the APOEε2 allele and genotype APOEε3/ε3.Crohn’s disease patients with the APOEε2 allele scored lower on the Pediatric Crohn’s Disease Activity Index at diagnosis(P=0.0204).IBD patients with APOEε2 allele spent fewer days in the hospital due to relapse(P=0.0440).CONCLUSION APOE polymorphisms are associated with the risk of developing IBD and the clinical expression of IBD.However,the clinical relevance of the differences identified is rather modest.

A Study on Apolipoprotein E Polymorphism in Early Onset of Coronary Heart Disease

Objective :To assess the relationship between apolipoprotein E(apoE) polymorphism and early onset of Coronary heart disease(CHD) and the effect of apoE on lipids and tipoproteins in Chinese healthy subjects. Methods:Sixty-eight cases (CHDl) aged less than 55 y, 136 coses (CHD2) aged more than 65y with CHD and 136 healthy subjects were enrolled and their -plasma levels of triglyceride(TG) , total cholesterol (TC) and high density Upoprotein cholesterol (HDL-C) were determined. The apoE genotypes were identified by polymerase chain reaction-restriction fragment lengths polymorphism. Results -apoE3/4 genotype and E4 allele frequency in CHDl were higher than those in CHD2 and healthy subjects and no difference was found between CHD2 and healthy subjects. Meanwhile the plasma levels of TC and low density Upoprotein cholesterol(LDL-C) were higher in CHD2 than in either CHDl or healthy subjects. Each apoE isoprotein has variable TC and LDL-C levels characterized by E2 (E2/2 + E2/3) <E3(E3/3) <E4(E4/4 + E3/4). Conclusion.apoE is one of the genetic factors that affect the TC and LDL-C levels and apoE4 may be an independent genetic factor of early onset of CHD.

APOLIPOPROTEIN E POLYMORPHISM AND ALZHERMER'S DISEASE

We determined and analysed the ApoE polymorphism of 30 sporadic Alzheimer’s disease (AD) pa- tients, 27 patients with multi-infarct dementia (MID) and 46 aged healthy subjects as control. The results showed that the frequency of ApoE E4/3 genetype in AD group was significantly higher than that in con- trol (P<0. 05). Among these three groups, ApoE 4 allele frequency in AD group was significantly higher than that in control (P<0. 01 ) and MID group (P<0. 05). Among the three ApoE alleles, the risk ratio of ApoE E4 allele in AD group was 4. 114(p<0. 01 ). There was statistically significant (P<0. 05) as the increasing of ApoE 4 gene dose in AD. It suggests that ApoE is related to AD of Chineses and it might be a genetics index of early diagnosis for AD.

嗅三针对帕金森病痴呆小鼠海马CA1区载脂蛋白E和病理底物表达的影响

目的:观察嗅三针干预对帕金森病痴呆(Parkinson’s disease dementia,PDD)小鼠海马CA1区载脂蛋白E(apolipoprotein E,Apo E)、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)以及相关核心病理底物表达的影响,探讨嗅三针改善PDD认知功能的部分作用机制。方法:将雄性C57BL/6小鼠随机分为空白组(Control)、假手术组(Sham)、模型组(Model)和电针组(AE),每组10只;采用单侧内侧前脑束(medial forebrain tract,MFB)注射6-羟多巴胺(6-hydroxydopamine,6-OHDA)建立PD模型并筛选PDD小鼠。建模筛选成功后,电针组选取嗅三针进行电针治疗,各组小鼠干预14天后采用Morris水迷宫实验和穿梭箱实验评估各组小鼠学习记忆能力;HE染色观察海马CA1区细胞病理改变;免疫印迹法检测海马CA1区α-syn、Aβ、Apo E蛋白的表达;免疫荧光双标观察海马CA1区Apo E与GFAP的共定位率。结果:与模型组比较,电针组小鼠水迷宫逃避潜伏期缩短(P<0.01),穿越平台次数增加(P<0.05),穿梭箱主动回避次数增加(P<0.05),电击刺激平均时间减少(P<0.01)。模型组小鼠海马CA1区神经细胞排列稀疏、变性坏死,细胞核体积变小、浓染、结构不清,呈核固缩表现;而电针组小鼠海马CA1区神经元病变有明显改善,大部分细胞排列规则,细胞核圆而大,染色浅,形态清晰。电针组小鼠海马CA1区α-syn、Aβ、Apo E蛋白以及Apo E与GFAP共定位率均较模型组减少(P<0.01,P<0.01,P<0.01,P<0.05)。结论:嗅三针可提高PDD小鼠认知能力并改善神经元形态结构与功能,机制可能与其抑制星形胶质细胞Apo E表达从而减少海马CA1区α-syn、Aβ沉积有关。

ApoE基因多态性与冠心病的研究进展

冠心病严重威胁人类健康,近年由于人们生活方式等因素的影响,冠心病的发病率逐渐升高。血脂水平是影响冠心病发生的危险因素之一,而载脂蛋白E(ApoE)作为影响血脂水平的重要因素,在脂质代谢中具有重要作用。ApoE基因多态性可通过不同作用机制直接或间接影响冠心病的发生,全面了解ApoE基因多态性与血脂水平及冠心病的相关性,可以为临床冠心病的预防及早期诊疗提供参考,并可优化患者的治疗方案,减少治疗过程中不良反应的发生。

SLCO1B1和ApoE基因多态性与冠心病关系的研究

目的探讨溶质载体有机阴离子转运蛋白家族1B1(SLCO1B1)和载脂蛋白E(ApoE)基因多态性与冠状动脉粥样硬化性心脏病(冠心病)的关系。方法选取2020年1月至2022年6月于甘肃省武威肿瘤医院心血管内科收治的80例冠心病患者作为观察组,同一时间选取本院体检的80例健康者作为对照组,抽取外周血检测SLCO1B1和ApoE基因多态性,全自动生化分析仪检测血脂指标,Logistic分析冠心病的危险因素。结果对照组与观察组SLCO1B1基因型15/15、1a/15、1a/1a、1a/1b、1a/5、1b/15及1b/1b、等位基因15、1a、1b及5比较,差异无统计学意义(P>0.05)。观察组ApoE等位基因ε2及ε3的占比显著高于对照组(P<0.05)。与对照组相比,观察组患者SLCO1B1基因在1b/15型上总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)及载脂蛋白B(ApoB)水平升高,1a/15型TG水平升高,1a/1b型上高密度脂蛋白胆固醇(HDL-C)及载脂蛋白A1(ApoA1)降低,1b/1b型上TG升高,HDL-C及ApoA1降低(P<0.05)。与对照组相比,观察组ApoE基因在E2/E3型HDL-C降低,E3/E3型TG升高,HDL-C及ApoA1水平降低,E3/E4型HDL-C及ApoA1水平降低(P<0.05)。以冠心病为因变量,以上述结果中P<0.05的因素(高血压、糖尿病、TG、LDL-C、ApoA1、ApoB、ε3及ε4)作为自变量,运用Logistic回归分析结果发现,高血压、糖尿病、TG、LDL-C、ApoA1、ApoB及ApoE基因ε4型是诱发冠心病的危险因素(P<0.05)。结论SLCO1B1和ApoE基因多态性与血脂水平异常相关,ApoE基因ε4型可提高冠心病的发生。

Glaucoma and Alzheimer's disease:Their clinical similarity and future therapeutic strategies for glaucoma

Glaucoma refers to a group of diseases characterized by optic neuropathies that are commonly associated with degeneration of the retinal ganglion cells. Although intraocular pressure(IOP) is the only proven treatable factor, several studies indicate that other factors are involved in the pathogenesis of glaucoma. Since normal tension glaucoma(NTG) is the most common glaucoma at least in Japan and South Korea, development of new therapeutic strategies for glaucoma, besides reduction of IOP, is crucial. The clinical characteristics and mechanisms underlying neuronal degeneration in Alzheimer's disease, a progressive neurodegenerative disease, are similar to those of glaucoma. Impaired cerebral blood flow(CBF) is common to both these diseases;therefore, improving CBF may be considered a new treatment for glaucoma, especially for NTG. In addition, targeting the formation and aggravation pathway for amyloid-β and administration of apolipoprotein E-containing lipoproteins may be potential strategies for glaucoma treatment.

APOE基因与安徽地区冠心病血脂及冠脉病变程度的关系

目的:探究APOE基因与安徽地区冠心病血脂及冠脉病变程度的关系。方法:选取100例冠心病血脂异常患者为观察组,50例健康成人为对照组,行APOE基因型检查,比较两组及不同基因型组的血脂水平分布。结果:冠心病患者TC、TG和LDL-C水平升高,HDL-C水平降低。高血脂患者中,APOEε3型占比最高,APOEε2型最低。ε4型冠心病患者的TC和LDL-C水平高于ε2、ε3型,而ε2型冠心病患者的TG水平高于ε3、ε4型。不同冠状动脉病变程度的APOE基因型存在差异。结论:安徽地区,APOE不同等位基因型之间血脂水平有差异,且其不同基因型与冠状动脉病变程度有关。