淀粉样蛋白Aβ1-42在阿尔茨海默病中的意义

目的 :探讨老年人阿尔茨海默病 (Alzheimer’sdisease ,AD)脑脊液淀粉样蛋白Aβ1 - 42 的含量及其意义。方法 :采用ELISA法检测 30例AD ,非AD痴呆患者 2 5例和对照组 2 1例患者脑脊液中Aβ1 - 42 的浓度。结果 :AD患者脑脊液中Aβ1 - 42 水平明显低于非AD痴呆和对照组。结论 :Aβ1 - 42 在AD的发病中起重要作用 ,脑脊液Aβ1 - 42 值对AD的诊断具有一定的临床应用价值     

脑脊液中β-淀粉样蛋白检测与阿尔茨海默病的早期诊断

目的：检测β—淀粉样蛋白(β—amyloid protein，Aβ)两种主要成分Aβl-40和Aβ1—42在阿尔茨海默病(Alzheier's Disease，AD)脑脊液中的变化，并探讨其对AD的诊断价值。方法：采用敏感的双抗体夹心酶联免疫吸附法(ELISA)，检测54例AD患脑脊液中Aβ的浓度，并与30例正常对照(normal controls，NC)脑脊液中的相应成分进行对比。结果：①AD患脑脊液中Aβ1—42浓度低于正常对照组，而Aβl-40／Aβl—42比值高于对照组；②以脑脊液中Aβ比值及Aβl—42浓度检测诊断AD的敏感性分别为54．51％、90．00％，特异性为84．25％、84．38％。结论：临床上同时检测脑脊液中Aβl—42浓度及Aβ比值可作为早期诊断AD的辅助指标，具有一定的临床应用价值。     

脑脊液中Tau蛋白及Aβ检测对老年期痴呆早期诊断的意义

目的:探讨脑脊液(cerebrospinalfluid,CSF)中Tau蛋白及β-淀粉样蛋白(β-amyloidprotein,Aβ)对老年期痴呆(seniledementia,SD)主要包括老年性痴呆(Alzheimer'sdisease,AD)及脑血管病性痴呆(vasculardementia,VD)的诊断价值。方法:采用双抗体夹心酶联免疫吸附法(ELISA)检测54例AD患者,43例VD患者及30例正常对照者(normalcontrols,NC)脑脊液中Tau蛋白及Aβ1-42浓度。结果:老年期痴呆患者CSF中;①Tau蛋白浓度高于正常对照者(P<0.05);②Aβ1-42浓度低于正常对照者(P<0.05);③根据CSF中Tau蛋白、Aβ1-42浓度检测诊断老年期痴呆的灵敏度分别为51.55%、45.36%;特异性分别为90.90%、93.62%;结合Tau蛋白浓度及Aβ1-42浓度诊断SD的灵敏度为74.23%,特异性为93.33%。结论:临床上检测CSF中Tau蛋白、Aβ1-42浓度可作为早期诊断老年期痴呆的辅助指标。     

阿尔茨海默病患者脑脊液tau、Aβ_(1-40)、Aβ_(1-42(43))蛋白的检测及其临床意义

目的　探讨检测脑脊液tau、Aβ1-4 0 、Aβ1-4 2 (4 3 ) (以下简称Aβ1-4 2 )蛋白水平及其在阿尔茨海默病 (AD)诊断方面的意义。方法　用双抗体夹心ELISA法 ,共检测了 2 2例AD、15例脑血管性痴呆 (VD)和 30例非痴呆对照(NC)脑脊液中的上述 3种蛋白 ;用简单智能量表 (MMSE)、哈金斯基缺血量表 (HIS)、日常生活能力量表 (ADL)、CT和美国神经病、语言障碍和卒中 -阿尔茨海默病和相关疾病学会标准 (NINCDS -ADRDA)等判断受测者的认知情况 ,并作为临床分组诊断的依据。结果　AD、VD及NC组脑脊液tau、Aβ1-4 2 蛋白和Aβ1-4 0 /Aβ1-4 2 比值 (简称Aβ比 )存在显著差异 (P <0 .0 1或 0 .0 5 ) ,Aβ1-4 0 在各痴呆组与NC组之间变化不显著 (P >0 .0 5 )。结论　用双抗体夹心ELISA法可以在ng/L水平上检测人脑脊液tau和Aβ蛋白 ;在AD、VD及非痴呆老年人之间 ,脑脊液tau、Aβ1-4 2 蛋白存在明显的浓度梯度 ;检测老年期痴呆者脑脊液tau、Aβ1-4 2 蛋白和Aβ比可以作为生前诊断AD的一个有参考价值的生物学指标     

阿尔茨海默病与帕金森病认知功能和脑脊液中Aβ42水平检测及相关性分析

目的比较正常组、阿尔茨海默病（AD）组与帕金森病（PD）组的智力、记忆功能,比较正常组、AD病组与PD组脑脊液中Aβ42水平,分析三组间智力、记忆功能与脑脊液中Aβ42水平的相关性。方法采用韦氏成人智力量表及韦氏记忆量表分别对30例正常组、30例AD组及30例PD组患者进行检测,采用酶联免疫吸附测定（ELISA）方法对三组患者脑脊液中Aβ42水平进行检测,对三组实验数据进行相关性分析。结果AD组与PD组的智力、记忆功能明显低于对照组（P〈0．05,P〈0．01）,且AD组的智力、记忆功能明显低于PD组（P〈0．01）;AD病组与PD组脑脊液中Aβ42水平明显低于正常对照组（P〈0．05）,且AD脑脊液中Aβ42水平组明显低于PD组（P〈0．01）;三组中Aβ42水平的降低程度与智力、记忆功能受损程度成正相关。结论智力和记忆的检测以及脑脊液中Aβ42水平的检测为AD和PD的鉴别诊断提供了依据。     

痴呆患者血清和脑脊液中炎前和抗炎细胞因子的变化

目的:研究炎前和抗炎细胞因子在不同痴呆患者血清和脑脊液中的变化并探讨其临床意义. 方法:2003-09/2005-08我院和台山市人民医院神经科就诊的70例老年痴呆患者作为观察对象,其中阿尔茨海默病(AD)30例、混合性痴呆(MD)15例、血管性痴呆(VD)25例. 用夹心式酶联免疫吸附法测定各组老年人血清和脑脊液中白介素-1β(IL-1β),白介素-6(IL-6),肿瘤坏死因子α(TNFα)和白介素1受体拮抗剂(IL-1ra)的水平. 结果:各痴呆组患者脑脊液中TNFα的水平较正常老年人有不同程度升高,而IL-1ra则不同程度降低(P＜0.05或P＜0.01);AD组患者脑脊液中IL-1β水平高于对照组(P＜0.05),IL-6含量较对照组却无增高;VD组患者脑脊液中IL-6水平虽显著高于对照组(P＜0.05),但IL-1β含量与对照组相比无增高; MD组患者IL-1β,IL-6水平较对照组均有增高(P＜0.01). 各痴呆组血清中IL-1β,IL-6,TNFα和IL-1ra的水平与正常老年人相比无差异. 相关分析显示不同痴呆患者血清与其相对应的脑脊液中炎前和抗炎细胞因子水平之间无相关. 结论:痴呆患者脑内炎前和抗炎细胞因子的变化可能是其神经病理损害因素.     

沂蒙山区阿尔茨海默病与淀粉样β蛋白及其前体基因的相关研究

目的　探讨阿尔茨海默病 (AD)与淀粉样 β蛋白 (Aβ)及其前体 (APP)基因的关系。 方法　研究 32例沂蒙山区AD患者 ,并设对照组 30例 ,检测脑脊液Aβ水平、APP基因表达量。 结果　AD组Aβ水平 (13.6 2 7±9.335 ) μg/L、APP表达量 (16 2 4± 2 98)拷贝 / μl。均明显高于对照组 (P <0 .0 1)。结论　痴呆程度与Aβ水平、APP基因表达量呈正相关。AD与Aβ、APP密切相关。但APP表达量在AD的诊断中不具特异性。     

阿尔茨海默病患者血清中巨噬细胞集落刺激因子

目的 寻找阿尔茨海默病（Alzheimers disease,AD)患者早期诊断和监视病情动态变化的血清检测指标。方法 检测70例AD患者、52例年龄匹配的健康人（对照组）和22例血管性痴呆（VAD）对照患者血清中巨噬细胞集落刺激因子（M－CSF）的水平,以及32例AD患者和20例年龄匹配的健康人（对照组）,血清中IL－1β、IL－6、肿瘤坏因子－α（TNF－α）水平,并结合AD虱的病情进行分析对比。结果 AD患者组血清中M－CSF水平显著高于对照组（P＜0.01)和VAD患者组（P＜0.05);血清M－CSF水平主要在AD早期（轻、中度痴呆阶段）升高,在AD晚期（重度痴呆）则处于正常水平。AD患者组血清中IL－1β水平明显高于对照组（P＜0.05),但血清中TNF－α和IL－6利于正常水平。结论 血清M－CSF水平的检测是一种方便,敏感的方法,可望作为AD患者早期诊断的生物学标志。     

CSF淀粉样蛋白β42和tau水平与AIDS痴呆综合征有关

AIDS痴呆综合征(AD C)可以并发阿尔茨海默病(AD)。因为AD的发病和风险与CSF的β淀粉样蛋白(1-42)(Aβ42)、总tau(t-tau)、磷酸化tau(p-tau)水平有关,因此对ADC、A D和对照者的上述指标进行检测。AD C患者CSF的Aβ42明显降低,而t-tau和p-tau的浓度升高,与A D患者相似,结果表明AD     

脑脊液中β淀粉样蛋白42和神经丝轻链蛋白水平与术后神经认知功能障碍的相关性:基于90例66～78岁患者

目的 检测β淀粉样蛋白42（Aβ42）和神经丝轻链蛋白（NFL）在老年患者脑脊液中的表达情况，并探讨其与患者发生术后神经认知功能障碍（PNCD）的相关性。方法 选取2017年1月~2018年12月在解放军301医院麻醉科接受脊椎-硬膜外联合麻醉下行髋关节或膝关节置换术的90例老年患者作为研究对象。采用ELISA 法检测脑脊液中Aβ42和NFL的浓度水平。于术前1 d和术后7 d采用简易认知状态评价量表（MMSE）对患者进行认知评估；采用相关神经认知功能测试后，以Z 值计分法判定患者是否发生PNCD。Spearman秩相关分析脑脊液Aβ42和NFL的表达与MMSE评分的相关性。采用受试者工作特征曲线（ROC）曲线分析脑脊液Aβ42和NFL水平对PNCD的预测价值。结果 90例老年患者中有38例术后发生PNCD，发生率为42.2%。PNCD组患者脑脊液Aβ42为1.96 ng/mL，明显低于非PNCD组的2.54 ng/mL（t=3.29，P<0.05）；而PNCD组患者脑脊液浓度值为4.59 ng/mL，明显高于非PNCD组（3.16 ng/mL）（t=3.72，P<0.05）。患者脑脊液Aβ42与MMSE分值存在正相关（r=-0.659，P< 0.05）；脑脊液NFL浓度水平与MMSE分值存在负相关（r=-0.626，P<0.05）。ROC曲线分析结果，脑脊液Aβ42和NFL预测PNCD的的曲线下面积(AUC)分别为为0.744和0.768，而二者联合预的ROC曲线下AUC为0.847。结论 PNCD患者术前脑脊液Aβ42和NFL明显高于非PNCD患者。脑脊液中Aβ42和NFL浓度水平均可预测老年患者PNCD的发生，联合二者的诊断价值更高。     

组胺对β淀粉样蛋白诱导PC12细胞阿尔茨海默病体外模型的保护作用

目的:观察组胺对β淀粉样蛋白1-42(Aβ42)诱导大鼠肾上腺嗜铬瘤(PC12)细胞损伤的改善作用及其相关的受体亚型。方法:运用PC12细胞,采用Aβ42构建阿尔茨海默病体外模型,以形态学和四甲基偶氮唑盐比色法为指标,观察细胞损伤和药物的改善作用。结果:Aβ42浓度依赖性诱导细胞损伤。组胺在10-7、10-6mol/L浓度时能显著改善Aβ42(5μmol/L)作用24h引起的细胞损伤,10-6mol/L保护作用最大。组胺10-6mol/L的保护作用能被组胺H2受体拮抗剂zolantidine,H3受体拮抗剂clobenpropit所逆转,但不能被H1受体拮抗剂苯海拉明所拮抗。结论:组胺能减弱Aβ42诱发的细胞损伤,可能与组胺H2,H3受体有关。     

Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease

Context  Alzheimer disease (AD) is characterized by pathological results at autopsy of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical diagnosis of AD is determined on the basis of medical history, cognitive symptoms, and exclusionary criteria. The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) -amyloid_1-42 and tau proteins. Objectives  To compare CSF -amyloid and tau levels in a new population of AD patients and controls. To perform a meta-analysis of studies of CSF -amyloid and tau levels in AD patients and controls. Design  Cross-sectional study of the comparison of baseline CSF -amyloid_1-42 and tau levels in AD patients and controls. Meta-analysis involved 17 studies of CSF -amyloid and 34 studies of CSF tau. Setting  Clinical research unit of the National Institute of Mental Health, Bethesda, Md. Patients  The Geriatric Psychiatry Branch evaluated AD patients as inpatients at the National Institutes of Health Clinical Center between May 1985 and January 2001. A total of 203 patients participated in this study (131 with AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD patients and 1481 controls. Main Outcome Measures  Levels of CSF -amyloid_1-42 were measured by a sandwich enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and a monoclonal detection antibody. Levels of CSF tau were measured with a standard commercial immunoassay. Results  Levels of CSF -amyloid_1-42 were significantly lower in the AD patients vs controls (mean [SD], 183 [121] pg/mL vs 491 [245] pg/mL; P<.001). Levels of CSF tau were significantly higher in AD patients (mean [SD], 587 [365] pg/mL vs 244 [156] pg/mL; P<.001). The cutpoints of 444 pg/mL for CSF -amyloid_1-42 and 195 pg/mL for CSF tau gave a sensitivity and specificity of 92% and 89%, respectively, to distinguish AD patients from controls, which is comparable with rates with clinical diagnosis. Meta-analyses of studies comparing CSF -amyloid and tau levels in AD participants and controls confirmed an overall difference between levels in these 2 groups. Conclusions  Alzheimer disease is associated with a significant decrease in CSF -amyloid_1-42 levels along with an increase in CSF tau levels. These findings suggest that the 2 measures are biological markers of AD pathophysiology. While these CSF measures may have a potential clinical utility as biomarkers of disease, the preliminary and retrospective nature of the findings, the absence of assay standardization, and the lack of comparison patient populations must be addressed in future studies testing the usefulness of these CSF measures for predictive, diagnostic, or treatment evaluation purposes.      

丁苯酞对阿尔茨海默病模型大鼠P38及ERK表达的影响及意义

目的 研究阿尔茨海默病模型大鼠P38、ERK的表达及丁苯酞对其影响和意义.方法 成年雄性SD大鼠60只,随机分为模型组、丁苯酞组及对照组,每组20只;通过向大鼠海马内注射Aβ_(1-42)建立阿尔茨海默病模型,喂养60d后用Y型迷宫检测大鼠学习记忆能力、免疫组织化学染色检测大鼠脑组织P38和ERK的表达.结果 与对照组比较,模型组大鼠学习记忆能力下降,其海马CA1区P38阳性细胞增多,皮层ERK表达减少,差异均有统计学意义(P＜0.01);与模型组比较,丁苯酞组大鼠海马Ca1区P38阳性细胞数明显减少,皮层ERK表达增多,差异有统计学意义(P<0.01).结论 丁苯酞改善阿尔茨海默病大鼠学习记忆能力可能与其抑制P38、增加ERK的表达有关.

Abstract：

Objective To determine the effect of butylphthalide on the expressions of p38 mitogen-activated protein kinase and extra-cellular signal regulated kinases (ERKs) in the brain tissue of rats with Alzheimer's disease (AD). Methods Sixty male adult rats were randomly divided to AD model group, butylphthalide group, and control group (n=20). AD models were established by injecting beta-amyloid protein 1 -42 into the hippocampus of rats. Sixty days later, the learning and memory abilities of the rats were evaluated using Y-maze test, and the expressions of p38 and ERKs in the brain tissue of the rats were measured by immunohistochemistry. Results Compared with the control group, the rats in AD model group exhibited significantly reduced learning and memory abilities, increased expressions of P38 in the hippocampus and lowered expression of ERK in the cortex (P<0.01). In comparison with the model group, the rats in the butylphthalide group showed significantly decreased P38-positive cells in the hippocampus and increased expression of ERK in the cortex (P<0.01). Conclusion Butylphthalide improves the learning and memory abilities of rats with experimental AD, the mechanism of which may involve inhibition of P38 expression and enhancement of ERK expression in the brain tissues.     

正常人群脑脊液Tau蛋白含量的定量分析

目的:探讨正常人群脑脊液(CSF)Tau蛋白含量的分布范围,为阿尔茨海默病(AD)的相关研究奠定基础.方法:采用双抗体夹心式ELISA技术,对20例正常对照(NC)组及20例非AD神经系统疾病(ND)组CSF-Tau蛋白含量进行检测及统计分析.结果:CSF-Tau蛋白含量NC组与ND组间比较、男女性别间比较、CSF蛋白正常组和增高组间比较差异均无显著性.以年龄因素作直线相关分析,NC组r=0.53(P<0.05),呈正相关.结论:正常人群CSF-Tau蛋白含量为(125.88±45.62)ng*L-1,并随着年龄的增长有缓慢增高的趋势,但与性别及CSF蛋白总量无关.     

阿尔茨海默病模型大鼠PDI及P53的表达及丁苯酞对其的影响

目的 研究阿尔茨海默病模型大鼠PDI、P53的表达及丁苯酞对其影响.方法 成年雄性SD大鼠60只,随机分为模型组、丁苯酞组及对照组,每组20只;通过向大鼠海马内注射Aβ1-42建立阿尔茨海默病模型,喂养60d后用Y型迷宫检测大鼠学习记忆能力、免疫组织化学染色检测大鼠脑组织PDI和P53的表达.结果 与对照组比较,模型组大鼠学习记忆能力下降,其海马CA1区PDI阳性细胞减少,皮层P53表达增加,差异均有统计学意义(P＜0.01);与模型组比较,丁苯酞组大鼠海马CA1区PDI阳性细胞数明显增加,皮层P53表达减少,差异有统计学意义(P＜0.01).结论 丁苯酞改善阿尔茨海默病大鼠学习记忆能力可能与其增加PDI、抑制P53的表达有关.     

痴呆与脑脊液Tau蛋白含量的关系

目的:探讨痴呆与脑脊液(Cerebrospinal fluid, CSF)Tau蛋白(神经元微管相关蛋白)含量之间的关系,为阿尔茨海默病(Alzheimer′s disease, AD)临床诊断提供生化依据.方法:采用双抗体夹心式ELISA技术,对AD组15例、血管性痴呆(Vascular dementia, VD)组15例、神经系统疾病(Neurologic disease, ND)组20例及正常对照(Normal control, NC)组20例CSF-Tau蛋白含量进行检测,并作比较分析.结果:AD组CSF-Tau蛋白含量明显高于其它各组,差异有高度显著性(P<0.01);AD三个不同临床阶段间及CSF蛋白总量正常组与升高组间比较,差异均无显著性(P>0.05);以CSF蛋白总量为因素作直线相关性分析,ND组r=0.16(P>0.05),无相关性;以年龄因素作直线相关性分析,NC组r=0.53(P<0.05),具有正相关性.结论:CSF-Tau蛋白含量检测对AD的临床诊断具有一定的参考价值.     

Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer’s disease and vascular dementia

Background An important aspect of Alzheimer’s disease (AD) is loss or impairment of cholinergic neurons. It is controversial whether there is a similar cholinergic impairment and cerebral deficit of acetylcholine (ACh) in the case of vascular dementia (VD). The purpose of this study was to explore the levels of ACh and choline (Ch) in the cerebrospinal fluid (CSF) of patients with AD and VD, and their possible relationship with cognitive impairment.Methods Twenty-two AD patients, twenty-two VD patients, and twenty normal controls were recruited and scored with a Mini-Mental State Examination (MMSE). CSF concentrations of ACh and Ch were measured using high-performance liquid chromatography with an electrochemical detector (HPLC-ECD) and the results were then compared to cognitive status.Results ACh concentrations in CSF of AD patients ［(10.7±5.1） nmol/L］ and VD patients ［(16.8±7.4） nmol/L］ were both significantly lower than in controls ［(34.5±9.0） nmol/L, t=10.67, P&lt;0.001; t=6.91, P&lt;0.001］. Both results correlated positively with MMSE scores (rs=0.88 and rs=0.85, respectively, P&lt;0.01). The CSF concentration of Ch was significantly higher in VD patients ［(887.4±187.4） nmol/L］ compared to AD patients ［(627.6±145.1） nmol/L, t=6.4, P&lt;0.001］ and controls ［(716.0±159.4） nmol/L, t=4.2, P=0.002］. CSF Ch concentration showed no difference between AD patients and normal controls, nor did it correlate with MMSE score in any of the three groups. Conclusions The positive correlation between ACh deficit and cognitive impairment suggests that ACh is an important neurotransmitter for memory. The similar decrease in ACh concentration in AD and VD patients may imply a similar pathogenesis for the process of cognitive impairment involved in these two disorders. The elevated CSF levels of Ch in VD patients compared to AD patients may be useful diagnostically. Cholinesterase inhibitors may be helpful not only for AD patients, but also for VD patients.