Prediction of Alzheimer's disease in mild cognitive impairment: a prospective study in Taiwan

The relationship between apolipoprotein E (ApoE) and clinical manifestations of mild cognitive impairment (MCI) has not been investigated in non-Caucasian populations. This prospective study was conducted in an ethnic Chinese population to evaluate the correlations of ApoE genotype, cognitive performance, medial temporal structure volumes, and clinical outcome in amnestic MCI. Twenty normal elders, 58 MCI, and 20 mild Alzheimer's disease (AD) patients received neuropsychological, MRI, and ApoE genotype assessments at baseline. Patients with MCI had intermediate cognitive performance and hippocampal volumes between those in normal and AD groups. In each diagnostic group, 4 carriers (E4+) consistently had smaller hippocampal volume than non-carriers (E4−) did. Nineteen MCI subjects (32.7%) converted to AD during the 3-year study period. Compared with MCI non-converters and E4− MCI converters, E4+ MCI converters had the smallest hippocampal volume. However, 4 was not a predictor for AD. Both cognitive performance and hippocampal volume were predictive for progression to AD. However, stepwise Cox regression model integrating both neuropsychological and radiological variables showed that global cognitive performance was the only significant predictor for AD. A poor global cognitive score may be more crucial than a small hippocampal volume in the prediction of AD.     

ApoE^-/-；SAP—Tg小鼠模型的构建

目的为研究SAP蛋白在动脉粥样硬化中的作用及机制,拟构建ApoE^-/-;SAP—Tg小鼠模型。方法分别选取6～8周龄的雄性ApoE^-/-小鼠与血清淀粉样蛋白P转基因（SAP—Tg）6周龄的雌性小鼠杂交,得到的杂交后代以剪尾方式提取基因组DNA,用PCR法检测小鼠的基因型。结果雄性ApoE^-/-小鼠与雌性SAP-Tg小鼠杂交得F1代后自交,在F2代获得ApoE^-/-;SAP—Tg基因型小鼠,模型构建成功。结论将ApoE^-/-小鼠与SAP—Tg小鼠杂交2代后成功建立了ApoE^-/-;SAP—Tg小鼠模型,并可通过筛选出的F2代ApoE^-/-小鼠和ApoE^-/-;SAP—Tg小鼠交配进行繁育筛选工作。     

5-HT6基因多态性与阿尔茨海默病的相关性研究

目的探讨中国黑龙江地区汉族人群中5-HT6基因多态性与阿尔茨海默病（AD）的相关性。方法应用限制性片段长度多态性（RFLP）技术和聚合酶链反应（PCR）,在95例正常对照人群和105例阿尔茨海默病患者中观察5-HT6 基因多态性的分布,并探讨它们与阿尔获海默病之间的关系。结果在受试人群进行载脂蛋白E（ApoE）基因分型后,非ApoEε4型与ApoEε4型人群中AD与5-HT6受体基因各基因型或等位基因均无关联（P〉0．05）,AD组5-HR受体基因和C/ 基因型明显高于对照组,两组间差异有统计学意义（P〈0．05）。结论中国黑龙江地区汉族人群中5-HT。受体基因多态性与非ApoEε4型阿尔茨海默病相关联。     

Anti-atherosclerotic effects of Polygonum aviculare L. ethanol extract in ApoE knock-out mice fed a Western diet mediated via the MAPK pathway

Ethnopharmacological relevance

Polygonum aviculare L. has been used in traditional Korean medicine to treat obesity and symptoms associated with hypertension. The effectiveness or mechanism of Polygonum aviculare L. ethanol extract (PAE) on atherosclerosis disease has not been examined experimentally. This study investigated the protective effect of PAE in atherosclerotic mice.

Materials and methods

ApoE KO mice were fed a Western diet (WD) alone or with PAE or a statin for 12 weeks, followed by analysis of bodyweight, serum lipid levels, and blood pressure. Staining of the aorta and adipose tissue, expression levels of adhesion molecules, and the MAPK pathway were also examined. Cell viability, NF-κB activity, and protein levels of adhesion molecules were assessed in vitro.

Results

ApoE KO mice fed PAE (50 and 100 mg/kg) or statin (10 mg/kg) gained less body weight, and has less adipose tissue and lower serum lipid levels and blood pressures than the WD group. Aorta ICAM-1, VCAM-1, and NF-κB levels were decreased by PAE in a dose-dependent manner, consistent with the in vitro observations. PAE and statin decreased atherosclerotic plaque and adipocyte size versus the WD group. Furthermore, PAE decreased phosphorylation of MAPK pathway components in the aorta of PAE-treated mice, suggesting that PAE's anti-atherosclerotic effects are mediated via a MAPK pathway-dependent mechanism.

Conclusions

PAE may protect against the development of atherosclerotic disease. The beneficial effects are associated with lowering bodyweight, serum lipids, blood pressure, adhesion molecular protein levels, atherosclerotic plaque, and adipocyte size, involving the MAPK pathway.     

调脂通脉颗粒对ApoE基因敲除小鼠血脂及sICAM-1、sVCAM-1的影响

目的:探讨调脂通脉颗粒对载脂蛋白E(ApoE)基因敲除小鼠血脂、动脉粥样斑块及黏附分子的影响。方法:6周龄雄性ApoE-/-小鼠随机分为模型组、血脂康组、调脂通脉颗粒低中高剂量组,C57BL/6小鼠作为对照组,每组8只,高脂饮食结合药物喂养12周,血清检测观察血脂变化,主动脉弓根部石蜡切片苏木素伊红(HE)及马松(Masson)染色观察组织形态学变化,酶联免疫法(ELISA)检测血清可溶性细胞间黏附分子(sICAM-1)、可溶性血管细胞间黏附分子(sVCAM-1)表达。结果:血脂检测表明与正常对照组比较,调脂通脉颗粒各组、血脂康组、模型组小鼠血清总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平均显著升高(P<0.01),模型组、调脂通脉颗粒低剂量组小鼠血清甘油三酯(TG)水平明显升高(P<0.01);HE、Masson染色表明对照组主动脉内膜光滑未见粥样斑块形成;模型组主动脉内膜增厚伴易损斑块形成;血脂康组及调脂通脉颗粒高剂量组内膜增厚伴稳定斑块形成。ELISA法检测表明与正常组比较,调脂通脉颗粒各组、血脂康组、模型组小鼠血清sICAM-1、sVCAM-1水平显著升高(P<0.05),与模型组比较,调脂通脉颗粒高剂量组小鼠血清sICAM-1、sVCAM-1水平显著降低(P<0.05)。结论:调脂通脉颗粒可在一定程度上降低血清TG及sICAM-1、sVCAM-1水平,从而减缓AS病变。     

Glucose metabolism and gray-matter concentration in apolipoprotein E ε4 positive normal subjects

Apolipoprotein E (ApoE) ε4 is known as a genetic risk factor for Alzheimer's disease (AD). This study investigated the prevalence of imaging abnormalities suggestive of AD in cognitively normal ApoE ε4 carriers using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM). Forty-five cognitive normal ApoE ε4 allele carriers and 45 noncarriers underwent both FDG positron emission tomography and magnetic resonance imaging (MRI). A total of 90 normal database sets were generated for the individual 45 ε4 carriers and 45 noncarriers. Mean z-scores in the predefined AD-specific regions of interest (ROI) were calculated for each ε4 carrier and noncarrier using the individually defined normal database. The prevalence of AD-like hypometabolism and atrophy in the ε4 carriers was 8.9% and 17.7%, respectively, and did not differ significantly from those in the noncarriers (8.9%, 8.8%). The majority of ε4 carriers showed preserved FDG uptake or gray matter concentration.     

The role of extracerebral cholesterol homeostasis and ApoE e4 in cognitive decline

We examined the associations between extracerebral markers of cholesterol homeostasis and cognitive decline over 6 years of follow-up, and studied the modifying effect of apolipoprotein E (ApoE) e4. Data were collected in the Longitudinal Aging Study Amsterdam (n = 967, with longitudinal data on cognition, ages ≥ 65 years) and analyzed using linear mixed models. General cognition (Mini-Mental State Examination; MMSE), memory (Auditory Verbal Learning Test), and information processing speed (Coding task) were measured. The results show that ApoE e4 was a significant effect modifier. Significant associations were found only in ApoE e4 noncarriers (n = 718). We found a nonlinear negative association between the ratio of lanosterol to cholesterol (≤ 189.96 ng/mg), a marker for cholesterol synthesis, and general cognition. Lower cholesterol absorption, i.e., lower ratios of campesterol and sitosterol to cholesterol, as well as a higher rate of cholesterol synthesis relative to absorption were associated with lower information processing speed. In ApoE e4 carriers, the negative association between the ratio of campesterol to cholesterol and memory reached borderline significance. Future research should focus on the interaction between (disturbed) cholesterol homeostasis and ApoE e4 status with respect to dementia.     

金纳多对轻中度血管性痴呆患者ApoE、Hcy及认知功能的影响

目的：探讨金纳多治疗轻中度血管性痴呆的疗效及安全性。方法：随机选取63例符合DSM-IV血管性痴呆(VD)诊断标准的轻中度VD患者（MMSE评分在10～26分之间）;分别于金纳多治疗前、治疗后6周及12周,用MMSE和ADL量表评定患者的认知功能、社会活动功能及日常生活能力;用药前及用药后12周,用TCD检测脑血流;用...     

ApoE在脑血管狭窄患者血清中的含量及其在狭窄血管组织中的分布

目的 研究不同脑血管狭窄患者血清中总载脂蛋白E的含量,并观察其在狭窄脑血管部位的分布,探索ApoE在脑血管狭窄中的可能作用机制.方法 通过酶联免疫吸附试验检测患者血清中的ApoE含量;通过尸检,常规病理HE染色鉴定脑血管标本中的狭窄部位,并采用免疫组织化学的方法分析ApoE在相应部位的分布.结果 血清中总ApoE的检测...