苯扎贝特治疗儿童ApoE Tokyo(Arg25Cys)突变型脂蛋白肾病1例

脂蛋白肾病(Lipoprotein glomerulopathy,LPG),1989年首次由日本学者Saito报道,LPG主要累及肾脏,且以肾小球病变为主[1]。几乎所有患者均有不同程度的蛋白尿,多数表现为肾病综合征,少数表现为轻微蛋白尿和镜下血尿,部分患者伴有不同程度的贫血及高血压,血脂异常易被忽略为肾病综合征的低蛋白血症所致。载脂蛋白E(apolipoprotein E,ApoE)增高是LPG血脂改变的主要特点[2-3]。LPG为一种与脂质代谢紊乱密切相关的肾脏疾病,目前世界范围内有报道的病例不足200例,儿童报道仅10余例[2]。本病进展缓慢,临床常误诊为原发性肾病综合征[4]。因此,为增强对LPG的认识,提高诊治水平,现分析1例确诊的儿童LPG临床资料,总结LPG的临床特点、诊断、治疗及预后。     

慢性精神分裂症患者认知功能与ApoE基因的关联研究

目的：探讨慢性精神分裂症患者的易感性及其认知功能与ApoE基因之间的关系．方法：随机抽取61例住院的慢性精神分裂症病人作研究，以90例正常人作对照．用聚合酶链式反应（PCR）扩增技术及限制性片段长度多态性（RELPs）技术测定所研究对象的ApoE基因型和等位基因．结果：发现慢性精神分裂症与ApoE基因含等位基因ε3的基因型呈负关联，与等位基因ε2呈正关联，而认知功能与ApoE基因的基因型及等位基因均无关联．结论：ApoE基因与慢性精神分裂症的易感性有关，含等位基因ε3的基因型是慢性精神分裂症的保护因子，等位基因ε2是慢性精神分裂症的风险因子，而ApoE基因在慢性精神分裂症认知功能障碍的发生中不起重要作用．     

Diagnostic challenges of using CSF assay of tau and beta-amyloid42 in atypical degenerative dementias of the Alzheimer type

This report presents three cases of atypical degenerative dementias in order to illustrate challenges associated with the use of biologic markers of Alzheimer's disease (AD) for diagnosis and management. Clinical diagnostic methods followed the NINCDS-ADRDA criteria for AD. Additional diagnostic studies included serial neurocognitive testing, MRI, neuroSPECT, ApoE genotyping, and a CSF assay of tau and beta-amyloid(42). For patient 1, both the clinical and biologic markers were consistent with AD. The patient was diagnosed with AD with a high degree of confidence, even though the base rate of nonfamilial AD at this age group (<55 years) is exceedingly rare. This case argues favorably for the use of biologic markers to aid in confirming a diagnosis in an atypical dementia. Patient 2 met the NINCDS-ADRDA criteria for AD, although with less confidence. Neurocognitive data indicated a progressive right hemispheric syndrome, insight was preserved, and ApoE was 3/3, but tau concentrations and beta-amyloid(42) were highly consistent with cut-offs for AD; the differential fell on the Pick's disease/frontotemporal degeneration spectrum. Patient 3 had no clinical evidence of the disease, even when evaluated via extensive neurocognitive testing over a 2-year interval. However, ApoE was 4/4, and CSF assay of tau and beta-amyloid(42) were within the AD range. Therefore, while the CSF assay of tau and beta-amyloid(42) markers was confirmatory of AD, each case was highly atypical. Results illustrate the lack of normative data available when using biologic markers for highly atypical cases, calling into question their usefulness for such patients. These cases illustrate the interplay between neuropsychological and biological markers in establishing neurodegenerative diagnoses.     

Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers

The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction.     

何首乌总苷对ApoE-/-小鼠动脉粥样硬化病变形成的影响

目的:研究何首乌总苷(polygonum multiflorum total glycoside,PMTG)对载脂蛋白E基因缺陷(ApoE-/-)小鼠实验性动脉粥样硬化(atherosclerosis,AS)病变形成及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)与血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的表达影响,探讨何首乌总苷抑制AS病变形成的可能机制。方法:将ApoE-/-小鼠随机分为4组:何首乌总苷高剂量组(150 mg.kg^-1.d^-1)、低剂量组(25 mg.kg^-1.d^-1)、阿托伐他汀阳性药物组(5 mg.kg^-1.d^-1)及模型对照组。给药第10周后全部处死,检测4组血清脂质含量,一氧化氮(NO),总抗氧化能力(TAOC),丙二醛(MDA),主动脉AS粥样斑块面积及其与管腔面积的比值,主动脉壁ICAM-1及VCAM-1表达。结果:何首乌总苷高、低剂量组及阳性药物组与模型对照组ApoE-/-小鼠比较,显示:①何首乌总苷高、低剂量可以显著降低血清总胆固醇(TC),甘油三酯(TG)水平(P<0.01),升高高密度脂蛋白(HDL)水平(P<0.01);②明显增加血浆NO及TAC(P<0.05及P<0.01),减少MDA的生成(P<0.01);③何首乌总苷可减轻AS病变,减小斑块面积与管腔面积比值(P<0.05);④何首乌总苷可下调ICAM-1及VCAM-1的表达(P<0.01)。结论:何首乌总苷可能通过调节ApoE-/-小鼠血脂代谢、增强其抗氧化能力及下调主动脉壁ICAM-1及VCAM-1表达等上述环节的共同作用与影响,阻止ApoE-/-小鼠实验性动脉粥样硬化病变形成的发生、发展。     

江苏汉族人群心脑血管病患者载脂蛋白E基因研究

目的:探讨用基因测序法检测载脂蛋白E(ApoE)基因多态性及其与心脑血管疾病之间的关系。方法:应用基因测序方法检测了193例心脑血管疾病患者和100例无血缘关系的健康汉族人群ApoE基因型。结果:ε3/3基因型高血压组频率为64.3%,高血压 冠心病组为57.7%,高血压 脑血管病组为62.2%均明显低于对照组的86%(P<0.05);而ε3/4基因型频率,高血压组为21.4%,高血压 冠心病组为19.2%,高血压 脑血管病组为24.4%,均显著高于对照组的6%(P<0.05);ε4/4基因型高血压 冠心病组频率为5.1%明显高于对照组0%(P<0.05)。分析等位基因频率,高血压组和高血压 冠心病组、高血压 脑血管病组ε3等位基因频率分别为80.7%,74.4%和78.9%,明显低于对照组92.5%(P<0.05),ε4等位基因频率分别为12.1%,16.7%和14.5%,明显高于对照组的3.5%(P<0.05),差异有明显统计学意义。两组间其它各基因型无统计学差异。结论:应用基因测序方法进行ApoE基因分型是最全面、最直接、可靠的方法;ε4等位基因是心脑血管疾病共同的遗传易患因子,而ε3等位基因具有保护作用。     

青蒿素对ApoE-/-基因敲除小鼠动脉粥样硬化的影响

目的探讨青蒿素对ApoE-/-基因敲除小鼠动脉粥样硬化以及炎症因子的影响。方法将20只ApoE-/-基因敲除小鼠分为青蒿素组和PBS处理组,每组10只,经高脂喂养8周,与对照组小鼠(C57BL/6J标准饮食小鼠,10只)比较,通过血管大体油红O染色评价斑块面积;HE染色观察病变形态及血浆中炎症因子的变化。结果与对照组比较,PBS处理组及青蒿素组均可见动脉硬化斑块,炎症因子水平升高。青蒿素组的动脉硬化程度及炎症因子水平均明显低于PBS处理组。结论青蒿素可以改善ApoE-/-基因敲除小鼠动脉粥样硬化进展。     

APOLIPOPROTEIN E PHENOTYPE IN DEMENTED PATIENTS IN GREEK POPULATION

Apolipoprotein E is a plasma protein, involved in the transport of lipids and their metabolism. The aim of this investigation was to correlate the ApoE phenotypes with the type and the severity of dementia in Greek demented patients.

The investigation revealed that 72% of the patients have the E3/3 phenotype, but only 11% of them demonstrated the E3/2; 13% of the patients have the E4/3 phenotype and only 4% of them demonstrated the phenotype E4/4. The most severely demented patients corresponded to e4 alléle. The present results indicate that the most common ApoE phenotype in Greek demented patients is E3/3.     

The ApoE4 genotype modifies the relationship of long-term glycemic control with cognitive functioning in elderly with type 2 diabetes

AimTo assess whether the APOE4 genotype affects the relationship of long-term glycemic control with cognitive function in elderly with type 2 diabetes (T2D).MethodsParticipants were cognitively normal and pertained to a Diabetes Registry which provided access to HbA1c levels and other T2D related factors since 1998. Glycemic control was defined as the mean of all HbA1c measurements available (averaging 18 measurements) per subject. Four cognitive domains (episodic memory, semantic categorization, attention/working memory and executive function), based on factor analysis and an overall cognitive score (the sum of the 4 cognitive domains) were the outcome measures.ResultsThe analysis included 808 subjects; 107 (11.9%) subjects had ≥1ApoE4 allele. In ApoE4 carriers, higher mean HbA1c level was significantly associated with lower scores on all cognitive measures except attention/working memory (p-values ranging from 0.047 to 0.003). In ApoE4 non-carriers, higher mean HbA1c level was significantly associated with lower scores on executive function, but not with other cognitive measures—despite the larger sample size. Compared to non-carriers, there were significantly stronger associations in ApoE4 carriers for overall cognition (p=0.02), semantic categorization (p=0.03) and episodic memory (p=0.02), and the difference for executive function approached statistical significance (p=0.06).ConclusionIn this cross-sectional study of cognitively normal T2D subjects, higher mean HbA1c levels were generally associated with lower cognitive performance in ApoE4 carriers, but not in non-carriers, suggesting that ApoE4 affects the relationship between long-term glycemic control and cognition, so APOE4 carriers may be more vulnerable to the insults of poor glycemic control.     

APOE ε4: The most prevalent yet understudied risk factor for Alzheimer's disease

Brain pathology of Alzheimer's diseases (AD) and the genetics of autosomal dominant familial AD have been the “lamp posts” under which the AD field has been looking for therapeutic targets. Although this approach still remains valid, none of the compounds tested to date have produced clinically meaningful results. This calls for developing complementary therapeutic approaches and AD targets. The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic AD, and is expressed in more than half of the AD patients. However, in spite of its genetic prominence, the allele APOE ε4 and its corresponding protein product apoE4 have been understudied. We presently briefly discuss the reasons underlying this situation and review newly developed AD therapeutic approaches that target apoE4 and which pave the way for future studies.