ApoE 基因multi-ARMS 快速分型法

建立一种简单快速的ApoE基因分型法。以外周血细胞DNA为模板，设计了4个等位基因导性寡核苷酸引物和一个公共引物，采用等位基因特异性多重PCR技术（Multiplex Amplification Refractory Mutation System PCR,multi-ARMS PCR)，检测了85例个体的6种常见ApoE基因型。6种常见ApoE基因型的频率为：ε2/2(0.012),ε3/3(0.705)，ε4/4(0.012)，ε3/2(0.118)，ε4/3(0.141)和ε4/2(0.012）。本文简便、可靠，很有推广应用价值。     

配对盒4基因Arg121Trg多态性与2型糖尿病的相关性

目的 探讨配对盒4(Pax4)基因Arg121Trg多态性(rs114202595)与云南省昆明地区2型糖尿病的相关性.方法 根据口服75 g葡萄糖耐量试验(OGzTT)将1 076例云南省昆明地区人群分为2型糖尿病组(T2DM)、糖耐量减低组(IGT)和健康对照组(NGT),应用高分辨率熔解曲线分析方法(HRM)检测Pax4基因Arg121Trg基因型,观察3组人群中基因型和等位基因的分布情况,同时分析T2DM人群中不同基因型相关临床变量的差异性.结果 1)Pax4基因Arg121 Trg GG基因型(Arg/Arg)及A等位基因(Trg121)在T2DM组中的频率分别为0.909和0.047,在IGT组中为0.935和0.035,在NGT组中为0.939和0.03.2)T2DM组Arg121Trg 多态性GA+ AA基因型(Arg/Trg+ Trg/Trg)人群胰岛素使用率显著高于GG基因型(Arg/Arg)人群(P=0.001),而其他临床变量在T2DM组中两种基因型人群间比较均无明显差异.结论 Pax4基因Arg121Trg多态性A等位基因可能是云南省昆明地区2型糖尿患者群胰岛β功能进展性紊乱的一个分子标记.     

广西巴马地区长寿老人ApoE基因多态性与认知功能的关系

目的研究广西巴马地区长寿老人载脂蛋白E(ApoE)基因多态性的分布及其与认知功能改变的关系.方法采用简易精神状态量表(MMSE)对112例90岁以上广西巴马地区长寿老人进行认知功能检查,并用限制性酶切片段长度多态性分析(PCR-RFLP)方法进行ApoE基因分型.根据MMSE得分将研究对象分为认知功能正常组和认知功能障碍组,比较两组人群的基因型、基因频率的分布特征.结果巴马长寿老人中发生认知功能障碍者占14.29%.长寿老人中ApoEε3/3基因型分布的百分比最大,其次是ε2/3,而ε4/4最少.ApoE各基因型和等位基因频率认知功能正常组和认知功能障碍组相比较,ε4等位基因频率认知障碍组明显高于认知正常组(P＜0.01),ε4基因携带者认知功能障碍发生率明显高于其他基因携带者.结论巴马地区长寿人群中,ApoEε3/3为最常见的基因型,而ε4/4最少;ApoE基因多态性与巴马长寿老人认知功能改变有关联;ApoEε4基因仍然是长寿老人认知功能障碍发病的危险因子,较低的ApoEε4等位基因频率可能是巴马地区长寿老人认知功能保存较好的原因之一.     

用PCR-RFLP方法检测动脉硬化性脑梗死患者的载脂蛋白E基因多态性分布

目的研究动脉硬化性脑梗死(ACI)患者中的载脂蛋白E(ApoE)基因的分布.方法利用聚合酶链式反应(PCR)技术扩增ApoE基因含编码112位和158位氨基酸的片段,并用限制性片段长度多态性(RFLP)技术对ACI患者和相应健康对照的ApoE基因进行分型,从而进行ACI与ApoE等位基因多态性的关联分析.结果ACI患者中ApoE等位基因ε4占28.30%,明显高于正常人对照组的7.64%,而等位基因ε3则占57.55%,低于正常人对照组的84.12%,均有极显著性差异(p<0.01).结论PCR-RFLP是一种快速有效的ApoE基因分型方法,ε4可能为ACI的易感因子,而ε3则为保护因子.     

胎儿生长受限新生儿脐血载脂蛋白E和低密度脂蛋白受体基因多态性分布频率的研究

目的 探讨脐血载脂蛋白E(ApoE)、低密度脂蛋白受体(LDL-R)基因多态性与胎儿生长受限(FGR)对汉族新生儿血脂的相互影响.方法 采用病例-对照研究方法, 取57例FGR新生儿及57例同期出生正常体重新生儿脐血,用等位基因特异性多重聚合酶链反应技术(mμlti-ARMS)检测ApoE基因多态性,用聚合酶链式反应-限制片长多态性技术(PCR-RFLP)检测LDL-R基因AvaII位点多态性,同时检测血脂水平.结果 (1)共检测到4种ApoE基因型,E2/2,E4/4未检测到.FGR组ApoE3/4基因型(17.5%)和ε4等位基因型(13.2%)频率显著高于对照组(8.8%,7.9%,P<0.05);FGR组LDL-R AvaII(+/+)基因型频率(19.3%)显著高于对照组(10.5%)(P<0.05),两组间A+和A-等位基因频率比较差异无显著性(P>0.05).(2)两组血脂水平比较差异无显著性(P>0.05).(3)在两组中,ApoE3/4基因型个体TC和LDL水平显著高于ApoE2/3基因型个体(P<0.05).(4)在两组中,AvaII(+/+)基因型个体TC和LDL水平显著高于AvaII(-/-)基因型个体(P<0.05).(5)同时拥有ApoE3/4和AvaII(+/+)基因型者TC和LDL水平较高,而同时拥有ApoE2/3和AvaII(-/-)基因型者血胆固醇值均较低.结论 ApoE和LDL-R基因可能独立的影响脐血脂水平,新生儿中存在ε4或/和A+等位基因的个体发生高脂血症的风险增高.     

ApoE基因多态性与长寿及长寿相关表型的关联研究及Meta分析

目的 该研究在多群体中筛查验证ApoE基因多态性与长寿的关联,并调查ApoE基因变异与长寿相关表型的关联.方法 该研究采用群体1筛查,群体2、3验证的策略,共收集814个长寿老人(年龄≥90岁)和1136个无长寿家族史、当地一般人群的对照组(年龄30～65岁).通过PCR-RFLP和测序方法对ApoE基因进行基因分型.结果 在3个群体中长寿老人的ApoE ε3/ε3频率明显高于对照人群,与长寿存在正关联,这个结果与以往其他群体的研究结果并不相同;而长寿老人中ApoE ε3/ε4 频率明显低于对照群体,与长寿存在负关联.同时,在长寿老人中,ApoE ε3/ε3携带者比未携带ApoEε3/ε3者的高密度脂蛋白水平高(F=6.970,P=0.005),ApoE ε4携带者(ε3/ε4和ε4/ε4基因型总和)比非ApoEε4携带者的总胆固醇和低密度脂蛋白水平高(F=4.810,P=0.003和F=4.21 8,P=0.012).另外,该文对世界不同群体进行Meta分析,结果显示ApoE ε4携带者与长寿负关联(合并OR=0.42,95%CI:0.36～0.49),是长寿的风险因素.ε3/ε3基因型与长寿正关联(合并 OR=1.47,95%CI:1.25～1.74),是长寿的保护因素.结论 多个群体验证ApoE ε3/ε3可能是长寿的保护因素,这与以往报道ApoE ε2/ε2是长寿保护因素的结果不同;而ApoEε4是长寿的风险因素.

Abstract：

Objective The present study is to identify and replicate the association of ApoE longevity in multi-populations, and observe the association of ApoE with longevity-related phenotype. Methods By multi-population design:identifying ApoE gene associated with longevity in population 1, and replicating ApoE gene associated with longevity in population 2 and 3. A total of 814 "longevity cases" were classified as participants who had survived to age 90 years or more, with a total of 1136" younger controls" less than 65 years of age. ApoE gene was genotyped by PCR-RFLP and sequencing. Results Results showed the homozygous ε3/ε3 genotype in long-lived population was significantly higher frequent than those in controls,positively associated with longevity, whereas the heterozygous ε3/ε4 genotype were significantly lower frequent than those in controls, negatively associated with longevity in 3 different populations. ApoE ε3/ε3 was associated with higher HDL-C levels(F=6.970,P=0.005),and ApoE ε4-carrier(the ε3/ε4 and ε4/ε4 genotypes) was associated with significantly higher TC and LDL-C levels(F=4.810,P =0.003 and F=4.218,P=0.012)in long-lived individuals.In addition, the meta-analysis in 14 populations in world suggested ε4-carriers were negatively associated with longevity(pool ORs=0. 42,95% CI:0. 36～0.49);whereas the ApoE ε3/ε3 genotype was positively associated (pool ORs=1.47,95% CI:1.25~1.74) with longevity. Conclusions It was confirmed ApoE gene was associated with longevity in multi-population. ApoE ε3 gene could conferred protective effect for healthy longevity which was inconsistent the previous results published , whereas ApoE ε4 gene increased the risk effect for successful aging and longevity.     

SLCO1B1/ApoE基因多态性与瑞舒伐他汀疗效及安全性的相关性研究

目的 探讨SLCO1B1与ApoE基因多态性对瑞舒伐他汀的降脂疗效和安全性的相关性.方法 采用纳米磁珠法提取全血基因组DNA,PCR-焦磷酸测序法检测SLCO1B1与ApoE基因多态性.152名受试者口服瑞舒伐他汀10 mg/d,通过检测用药前以及用药8周后的低密度脂蛋白胆固醇(LDL-C)水平,评价降脂疗效;通过随访用药期间肌痛的发生,评价肌病不良反应的发生频率.结果 152名受试者SLCO1B1 521T＞C基因型分布为TT 73.7％,TC 23.7％,CC 2.6％;ApoE基因型分布为ε3/ε3 65.8％,ε3/ε213.2％,ε4/ε3 21.0％,未见ε4/ε4、ε2/ε2、ε4/ε2基因型.瑞舒伐他汀治疗8周后,APOE ε3/ε3,ε3/ε3与ε4/ε3基因组比较,患者血浆中的LDL-C下降水平有统计学意义(P＜0.05);SLCO1B1 521T＞C 3种基因型发生肌痛的频率明显不同(P＜0.05).结论 SLCO1B1/ApoE基因多态性与瑞舒伐他汀疗效及安全性具有相关性,联合检测SLCO1B1与ApoE基因型有助于预测疗效和不良反应,实现瑞舒伐他汀的个体化用药.     

冠心病患者焦虑情绪与APOE基因多态性

目的:探讨冠心病(coronary heart disease,CHD)患者焦虑情绪与载脂蛋白E(ApoE)基因多态性的关系。方法:对符合1979年世界卫生组织CHD诊断标准的107例冠心病患者,进行汉密顿焦虑量表(Hamilton Anxiety Scale,HAMA)、焦虑自评量表(Self-Rating Anxiety Scale,SAS)测评,依焦虑评分情况将患者分为CHD伴焦虑组(焦虑组)、CHD不伴焦虑组(无焦虑组),选择53例健康人为对照组。于入院2日内留存血样,以Hhal限制性内切酶酶切及琼脂糖凝胶电泳确定ApoE基因多态性,采用生物化学方法测定血清血脂。结果:焦虑组ε4等位基因频率高于无焦虑组和对照组(26.0%vs.10.4%,26.0%vs.13.6%;P=0.021,0.004)。焦虑组E4/4基因型频数高于无焦虑组(4vs.0,P=0.032)。焦虑组E3/4基因型频数高于对照组(17vs.8,P=0.018)。无焦虑组ε4等位基因频率高于对照组,但差异无统计学意义(13.6%vs.10.4%,P=0.802)。CHD组携带ε4等位基因患者HAMA[(13.2±5.2)vs.(9.2±6.5)]、SAS评分[(42.3±7.7)vs.(37.1±8.3)]及总胆固醇[(5.4±1.1)mmol/Lvs.(4.8±1.3)mmol/L]、低密度脂蛋白水平[(3.6±1.0)mmol/Lvs.(3.1±1.1)mmol/L]均高于非携带ε4等位基因者(P0.05)。结论:冠心病患者的焦虑情绪可能与ApoE基因多态性具有一定关系。ApoEε4等位基因可能是CHD患者焦虑情绪的危险因素。     

XRCC1、hOGG1基因多态性与喉癌遗传易感性的关系

目的 探讨X线修复交叉互补组1基因(X-ray repair cross complementing group 1,XRCC1)、8-羟基鸟嘌呤修复酶基因(human 8-oxoguanine glycosylase I,hOGG1)多态性与喉癌遗传易感性的关系.方法 采用病例-对照设计,应用聚合酶链反应-限制性片段长度多态性分析法检测了72例经病理确诊的喉癌患者和随机抽样的72例无肿瘤、无遗传病对照者XRCC1-Arg399Gln、hOGG1-Ser326Cys多态性.结果 病例组XRCC1第399位密码子杂合型(Arg/Gln)及突变型(Gln/Gln)和hOGG1第326位密码子杂合型(Ser/Cys)及突变型(Cys/Cys)分布频率均高于对照组(P＜0.05),与携带XRCC1-399野生型(Arg/Arg)、hOGG1-326野生型(Ser/Ser)个体相比,携带该基因型的个体喉癌的发病风险分别升高了3.37和2.54倍.交互作用分析显示,吸烟组与不吸烟组相比,携带XRCC1、hOGG1各基因型的个体的喉癌发病风险差异未发现存在统计学意义(xH12=0.15,xH22=0.28,P＞0.05).结论 XRCC1-399位点Arg→Gln和hOGG1-326位点Ser→Cys的氨基酸替换可能导致喉癌的发病风险增加,XRCC1-Arg399Gln、hOGG1-Ser326Cys多态性可能与喉癌的遗传易感性有关.     

新疆维吾尔族阿尔茨海默病患者脑啡肽酶基因与载脂蛋白E基因多态性的关联分析

目的 探讨脑啡肽酶(neprilysin,NEP)基因rs3736187位点突变及其与载脂蛋白E(apolipoprotein E,ApoE)基因相互作用在新疆维吾尔族人群散发性阿尔茨海默病(sporadic Alzheimer disease,SAD)发病机制中的作用.方法 应用聚合酶链反应-限制性片段长度多态性方法 检测了111例维吾尔族SAD患者和117名维吾尔族正常老年人NEP基因和ApoE基因多态性分布特征.结果 (1)NEP基因T等位基因频率在AD组高于对照组(x2=5.005,P＜0.05),携带T等位基因个体出现AD的危险性高于携带C等位基因的个体.(2)ApoE基因ε4等位基因频率AD组高于对照组(x2=4.218,P＜0.05),携带ε4等位基因个体出现AD的危险性高于未携带ε4等位基因的个体.(3)NEP基因的T等位基因与SAD发病相关且不受ApoE基因型影响.结论 NEP基因和ApoE基因的基因多态性与新疆维吾尔族SAD发病有关联.NEP基因可能是新疆维吾尔族SAD发病独立的易感基因.     

湖北省利川市土家族人群载脂蛋白E基因多态性及血脂水平的流行病学分析

目的:研究湖北省利川市土家族人群中载脂蛋白E(ApoE)基因型和等位基因频率以及ApoE表型与血脂水平之间的关系。方法:应用等位基因特异性多重聚合酶链反应技术(multi-ARMSPCR)对431例土家族健康人群的ApoE基因型进行分析,并测定所有样本血脂水平,对结果进行统计学分析。结果:ApoE各基因型频率分别为:ε2/2=0.464%、ε2/3=12.07%、ε2/4=1.62%、ε3/3=74.94%、ε3/4=10.21%、ε4/4=0.696%;各等位基因频率分别为ε2=0.0729、ε3=0.862、ε4=0.0651。频率分布与年龄、性别无关。国人ε3等位基因频率明显高于欧美人群,而ε4等位基因频率明显低于欧美人群。携带ε4等位基因的个体具有较高的总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平。结论:湖北省利川市土家族人群ApoE等位基因频率分布与中国其他地区汉族人群频率分布比较无显著性差异;与亚洲人群如日本、新加坡人群基本接近,与欧美人群不同。     

ApoE gene polymorphism and its relationship with coronary artery disease in ethnic Kashmiri population

Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.     

Apolipoprotein E genotypes and the risk of Parkinson disease

We examined apolipoprotein E (ApoE) genotypes in relation to Parkinson's disease (PD) among 786 cases and 1537 controls, all non-Hispanic Caucasians. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression models, adjusting for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Compared with participants with ApoE ε33, ε4 carriers (ε34/ε44) had significantly lower odds for having PD (OR, 0.75; 95% CI, 0.59-0.94; p = 0.01), whereas ε2 carriers (ε23/ε22) did not (OR, 0.95; 95% CI, 0.73-1.24; p = 0.71). Subgroup analyses showed similar results. In addition, we conducted a meta-analysis which confirmed our primary findings (ε34/ε44 vs. ε33: OR, 0.90; 95% CI, 0.81-0.99; p = 0.024 and ε23/ε22 vs. ε33: OR, 1.10; 95% CI, 0.97-1.23; p = 0.13). In PD patients, the prevalence of dementia appeared to be higher among ε4 carriers (compared with ε33: OR, 1.59; 95% CI, 0.98-2.58; p = 0.06), but lower among ε2 carriers (OR, 0.75; 95% CI, 0.40-1.42; p = 0.38), although neither test was statistically significant. Our study suggested that the ApoE ε4 allele may be associated with a lower PD risk among non-Hispanic Caucasians.     

肥胖者HDL亚类组成与载脂蛋白E基因多态性的关系

目的：探讨肥胖者血清载脂蛋白E基因多态性与HDL亚类组成的关系。 方法： 采用聚合酶链反应-限制性片段长度多态性和双向电泳-免疫印迹检测法，分析93例肥胖者和96例非肥胖者者的apoE基因型、HDL各亚类组成及相对含量。 结果： 肥胖组和对照组apoE基因型及等位基因频率分布均以E3/3和ε3最高。肥胖者等位基因ε2携带者血清apoE/CⅢ、HDL2a较等位基因ε3和ε4携带者升高，而apoB100、apoCIII、HDL3c则较ε3携带者下降，差异显著（P<0.05）。对照组中等位基因ε2携带者血清TC、apoE较等位基因ε3携带者升高，等位基因ε2携带者HDL3b较等位基因ε3携带者降低，差异显著（P<0.05）。 结论： apoE 基因多态性与HDL亚类的组成和分布相关,ε2等位基因有减缓肥胖者HDL颗粒变小的作用。     

Genetic study of Apolipoprotein E gene,alpha‐1 antichymotrypsin gene in sporadic Parkinson disease

Several lines of evidence have suggested some common genetic risk factors for Alzheimer disease (AD) and Parkinson disease (PD) because there are some overlapping pathologies in these two neurodegenerative diseases. In the present study, we investigated the role of Apolipoprotein E gene polymorphism and the signal peptide polymorphism in alpha‐1 antichymotrypsin (ACT) gene in idiopathic sporadic PD. The study was performed in a sample consisting of 68 PD cases and 160 healthy subjects in Shanghai China. We found no significant differences of ACT gene polymorphic distribution between PD cases and controls. The ApoE gene ε2/ε4 genotype was significantly more frequent in PD subjects (χ² = 7.126, df = 1, P = 0.008) and conferred a 12.70 times susceptibility for PD (OR = 12.62, 95% CI: 1.445–110.17, χ² = 5.259, P < 0.05, AF = 4.59%). No interaction of ApoE and ACT genes was detected in PD. Therefore, our data suggested that the ApoE ε2/ε4 genotype might be a susceptibility variant of moderate effect for sporadic idiopathic PD in our samples, whereas the ACT gene signal peptide polymorphism might not. © 2002 Wiley‐Liss, Inc.     

载脂蛋白E基因多态性与痉挛型脑性瘫痪的相关性研究

目的探讨中国汉族儿童痉挛型脑性瘫痪与载脂蛋白E基因多态性的关系。方法应用聚合酶链反应与限制性片断长度多态性分析方法对110例痉挛型CP患者和110例正常儿童的ApoE基因型和等位基因进行测定,并探讨ApoE基因多态性与痉挛型CP的关系。结果对照组和病例组ApoE基因型分布符合Hardy-Weinberg定律(P0.05),对照组与病例组的ApoE基因型和等位基因频率分布具有显著性差异(P=0.006,P=0.002),携带ε4等位基因与痉挛型CP呈显著性相关(χ2=11.973,P=0.001),携带ε4等位基因患CP的风险性提高6.253倍。结论 ApoE的ε4等位基因与痉挛型CP的发病相关,是痉挛型CP发病的遗传易感因子。     

Association of APOE ε2/ε3/ε4 and promoter gene variants with dementia but not cardiovascular mortality in old age

The common apolipoprotein E (APOE) alleles ε2, ε3, and ε4 are associated with the risk of dementia and cardiovascular disease. Recently, two functional variants (? 219G/T and ?491A/T) were identified in the promoter of the APOE gene that enable a further characterization of the role of the APOE locus in disease. We investigated the contribution of these APOE gene variants to dementia and cardiovascular mortality in old age using a population‐based cohort of 648 subjects aged 85 years and over (Leiden 85‐Plus Study). Genotypes containing an APOE ε4 allele were associated with a 4.1‐fold (95% CI, 2.2–7.7) increased risk of dementia as compared to the ε3/ε3 genotype in old subjects. Moreover, homozygosity for the ?219T allele was found to be associated with a 2.4‐fold (95% CI, 1.0–5.8) increased risk independently of ε2 and ε4; the ?491A/T variant was not associated with dementia. Over a 10‐year follow‐up period, the risk of cardiovascular mortality was not increased among ε4 carriers (RR, 0.6; 95% CI, 0.4–1.0) or ?219T homozygous subjects (RR, 1.1; 95% CI, 0.7–1.7), nor did it decrease among ?491T homozygous subjects (RR, 1.4; 95% CI, 0.6–3.1). In conclusion, both the APOE ε2/ε3/ε4 and the ?219G/T variant were identified as risk factors for dementia but not cardiovascular mortality in old age. Our results support the hypothesis that both the isoform and the amount of APOE may influence the risk of dementia. Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age. © 2001 Wiley‐Liss, Inc.     

Apolipoprotein E genotype influences spatial distribution of cerebral microbleeds

In cerebral amyloid angiopathy patients, microbleeds often cluster, mostly occipital, and are associated with apolipoprotein E (APOE) genotype. Microbleeds also frequently occur in the asymptomatic, general population. In this population, we investigated spatial distribution of microbleeds and whether this is influenced by APOE genotype. In 292 persons with microbleeds, we labeled microbleeds on baseline and follow-up magnetic resonance images. We calculated distance between incident and prevalent microbleeds within and between persons and performed lobar segmentation on the magnetic resonance images. Subsequently, we investigated proximity and lobar distribution in strata of APOE genotype. Microbleeds occurred closer within persons than between persons (−42.2 mm, 95% confidence interval, −44.6 to −39.9; p < 0.001). Microbleeds within APOE ε2 and ε4 carriers occurred closer than those in persons with ε3ε3 genotype (−11.9 mm, 95% confidence interval, −24.4 to 0.6; p = 0.06). Persons with ε2 and ε4 alleles had a larger proportion of microbleeds in the occipital lobe than persons with ε3ε3 genotype. Similar to cerebral amyloid angiopathy patients, microbleeds in the general population cluster and the distribution is affected by APOE genotype.