Alzheimer病和血管性痴呆患者血清β—AP与多肽生长因子相关性

目的:探讨血清β淀粉样蛋白(β－ＡＰ)和多肽生长因子含量变化及其相关性在Ａｌｚｈｅｉｍｅｒ病(ＡＤ)和血管性痴呆(ＶＤ)发病机制中的作用。方法:采用放免法检测ＡＤ患者３２例,ＶＤ患者３４例及６３例缺血性脑血管病(ＩＣＶＤ)患者血清β－ＡＰ、转化生长因子α(ＴＧＦ－α)和类胰岛素样生长因子Ⅱ(ＩＧＦ－Ⅱ)水平,与对照组比较。结果:ＡＤ与ＶＤ患者血清β－ＡＰ、ＴＧＦ－α、ＩＧＦ－Ⅱ水平明显高于ＩＣＶＤ组和对照组,有显著差异(Ｐ＜０．０１),两组患者血清β－ＡＰ和ＩＧＦ－Ⅱ之间呈明显相关关系。结论:①β－ＡＰ是ＡＤ和ＶＤ发病危险因素;②引起ＡＤ和ＶＤ神经元毒性作用进而导致痴呆与ＴＧＦ－α和ＩＧＦ－Ⅱ增多有关;③β－ＡＰ与ＴＧＦ－α、ＩＧＦ－Ⅱ密切相关,并在老年斑形成过程中起主要作用。     

Alzheimer病和血管性痴呆病人脑脊液中β淀粉样蛋白含量比较

目的研究脑脊液中β－淀粉样蛋白量的变化对Ａｌｚｈｅｉｍｅｒ病（ＡＤ）和血管性痴呆（ＭＩＤ）的临床诊断有无鉴别意义。方法用单克隆抗体、ＥＬＩＳＡ方法检测两种痴呆患者各１６例和健康对照组３１例脑脊液中β－淀粉样蛋白（ＡＰ１－４０）的含量。结果在年龄构成和痴呆程度无明显差异的ＡＤ和ＭＩＤ两组间，脑脊液中ＡＰ１－４０的含量有明显差异。ＡＤ组Ａ值为０．２１７～０．３８０，平均０．２７４；ＭＩＤ组为０．２４１～０．４９２，平均０．２９０；ＡＤ组明显低于ＭＩＤ组。对照组Ａ值为０．２２８～０．５６７，平均０．３１１，明显高于ＡＤ组（Ｐ＜０．０１）而与ＭＩＤ组间差别不明显（Ｐ＞０．０５）。结论根据本研究结果，对于临床已诊断为痴呆的病例，检测脑脊液中β－淀粉样蛋白的含量对ＡＤ和ＭＩＤ的鉴别可能有所帮助     

线粒体相关性β淀粉样前体蛋白及线粒体相关性β淀粉样蛋白针对阿尔茨海默病致病机制的研究

线粒体相关性β淀粉样前体蛋白(APP)和线粒体相关性β淀粉样蛋白(Aβ)正逐渐成为研究阿尔茨海默病(AD)病理生理学改变的热点。线粒体相关性APP和线粒体相关性Aβ是指以线粒体为特异性靶点,存在于线粒体膜上或沉积于线粒体基质内的APP和Aβ。文中将分别介绍线粒体相关性APP和线粒体相关性Aβ的来源、结构、功能等方面的研究进展,揭示其与AD发病的密切关系。     

大鼠前脑不全缺血再灌注后β-淀粉样蛋白的表达及意义

目的 研究不全缺血再灌注后AD表达的规律及意义。方法 结扎一侧颈动脉后剪断，另一侧夹闭2h后恢复血流。免疫组化方法研究再灌注不同时间点Aβ表达变化。结果 再灌注6hAβ表达无明显增加，4d开始增加，8d达到高峰。再灌注16d开始下降，35d继续下降趋于消失。结论 不全缺血再灌注后Aβ表达达到高峰后又趋于消失，神经系统存在维持Aβ代谢平衡的机制。Aβ表达可能解释VD患者出现的AD病理改变。     

β—淀粉样蛋白与Alzheimer病

Ａｌｚｈｅｉｍｅｒ病（ＡＤ）是以进行性痴呆为主要临床表现的中枢神经系统最常见的变性病。其病理特征为：（１）老年斑（ＳＰ）,散在于病变部位,由退变的神经轴突围绕β－淀粉样蛋白（β－ＡＰ）组成。（２）神经原纤维缠结（ＮＦＴ）,存在于病变部位的神经元胞浆内...     

β淀粉样蛋白代谢相关基因与阿尔茨海默病的研究进展

阿尔茨海默病(AD)是老年人常见的神经系统变性疾病,是痴呆中最常见的一种类型,目前认为β淀粉样蛋白(Aβ)的异常沉积是AD主要发病机制之一,然而,Aβ的异常沉积与Aβ代谢相关基因的表达异常密切相关。本文就Aβ代谢相关基因作一综述,并讨论其在AD早期诊断中的意义。     

阿尔茨海默病的淀粉样β蛋白前体基因的表达研究

】     

Alzheimer病与老年脑中β-淀粉样蛋白免疫组化的研究

目的探讨β－淀粉样蛋白（β－ＡＰ）与Ａｌｚｈｅｉｍｅｒ病（ＡＤ）、脑老化之间的关系。方法采用免疫组化方法检查经过临床与病理确诊的３例ＡＤ与６例非痴呆老年对照（ＮＡＤ）脑组织广泛部位中β－ＡＰ的沉积，并且与淀粉样蛋白组化染色的方法如刚果红、爱先蓝（ＳＡＢ）染色相对比。结果发现１ＡＤ脑组织中β－ＡＰ的沉积较ＮＡＤ不仅部位广泛，而且程度严重。２β－ＡＰ的免疫组化染色方法较淀粉样蛋白组化染色方法敏感而可靠。结论β－ＡＰ在脑中的沉积可能与神经元的变性以致智能衰退、ＡＤ的发生有关。β－ＡＰ的免疫组化检测可作为ＡＤ组织学诊断的重要参考。     

血清淀粉样蛋白P与阿尔兹海默病和血管性痴呆的相关性研究

<正>随着世界人口老龄化进程的快速发展,全世界每年新增990多万痴呆患者,截止2019年报告,目前世界上已有近5000万痴呆患者,2050年将增加至1.52亿例。据推算,2030年全球用于痴呆症的费用将达到2.54万亿美元,2050年为 9.12万亿美元^[1],给整个社会和患者家庭带来沉重的经济负担和心理负担。阿尔茨海默病(Alzheimer’s disease, AD)和血管性痴呆(vascular dementia, VD)是痴呆的两大主要类型,     

淀粉样β蛋白对表达的鼠脑乙酰胆碱受体功能的影响

目的 观察淀粉样β蛋白（Ａβ）表达的鼠脑乙酰胆碱（ＡＣｈ）受体功能的影响,探讨Ａβ和乙酰胆碱受体介导的阿尔茨海默病（ＡＤ）发病机理。方法 将提取的３个月龄鼠的脑乙酰胆碱受体ｍＲＮＡ注射到非洲爪蟾卵母细胞进行受体表达,采用双电极电压钳位技术记录表达的神经递质受体通道电流,了解其电流特性并观察淀粉样β蛋白１－４０（Ａβ１－４０）对其的影响。结果 表达到爪蟾卵母细胞膜上的ＡＣｈ受体为Ｍ型ＡＣh受体,其激     

Systemic amyloid deposition in old age and dementia of Alzheimer type: the relationship of brain amyloid to other amyloid

Summary We investigated amyloid deposition in the brain and other organs in 105 consecutive autopsy cases, aged 59 to 101 years. They consisted of two groups; 15 patients with dementia of Alzheimer type (DAT) and 90 patients without DAT. Amyloid deposition was found in 93% of all cases. The incidence of amyloid deposition increased with age. The number of organs affected with amyloid deposition in each case also increased with age. The incidence of amyloid deposition in each organ was as follows; 88% in pituitary gland, 66% in brain [amyloid of senile plaque (SP) (61%) and/or cerebral amyloid angiopathy (CAA) (56%)], 33% in pancreas, 3% in heart, and less in others. In immunohistochemical studies using the antisera to the various kinds of amyloid or related proteins, amyloid protein was demonstrated in brain amyloids including SP and CAA, but not in others. Cardiac amyloid was positive for prealbumin. Pituitary amyloid and CAA were positive for amyloid P-component. The incidence of brain amyloids in DAT were significantly higher than that in non-DAT. There was no significant difference in the incidence of pituitary and pancreatic amyloid between DAT and non-DAT. In the non-DAT patients, there were significant positive correlations in amyloid deposition between the brain and pituitary gland and between the brain and pancreas. Acceleration of amyloid deposition would be a process confined to the brain in the patients with DAT. The pathogenesis of the accelerated deposition of brain amyloids is discussed from the point of view of amyloidosis.Supported in part by the Research Committee on Primary Amyloidosis, Ministry of Health and Welfare, Japan     

Editor's note for debate Sporadic dementia of Alzheimer type: Role of amyloid in etiology is challenged

Summary Alzheimer's disease is a heterogenous neurodegenerative disorder. Whereas only a minority is due to genetic abnormalities and mostly with early onset, the majority of all Alzheimer cases is sporadic and with late onset. Therefore, in the latter, age-related disturbances in cellular metabolism may come into focus with respect to the etiopathogenesis rather than the primary formation of amyloid. In this Editor's note for debate, the role of amyloid as a causative factor of sporadic Alzheimer's disease is challenged. Instead, as a possible primary abnormal event in sporadic Alzheimer's disease, the perturbations in neuronal glucose metabolism and the subsequent ATP deficit with its impacts on the secondary amyloid formation are discussed to open a new field of research and another aspect for debate.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

目的 探讨铁调节蛋白2(IRP2)基因2616C/T多态性与阿尔茨海默病(AD)、血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性技术检测281例AD、60例VD患者及285名正常老年人的IRF2基因2616C/T多念性分布,并评定简易精神状态检查表(MMSE);将AD患者按临床痴呆评定量表(CDR)评分分为轻度痴呆组(CDR=1分,72例)和中重度痴呆组(CDR=2分或3分,209例),比较各组间IRP2基因2616C/T多态性.结果 (1)AD组与对照组基因型(χ2=2.46)及等位基因(χ2=2.17)总体分布差异无统计学意义(P>0.05);而中重度AD组携带T等位基因的基因型频率(78.0%)高于对照组(69.8%;χ2=4.106,P<0.05),Logistic回归分析其中携带含T等位基因的基因型患者的比值比=1.62(95%可信区间=1.03～2.54).VD组携带含T等位基因型频率和T等位基因频率虽高于对照组,但未达统计学意义(P>0.05).(2)中重度AD患者T/T基因型频率(25.8%)和T等位基因频率(51.9%)高于轻度AD患者(分别为12.5%和40.3%),差异均有统计学意义(χ2=5.477和5.803,P<0.05).(3)携带T/T基因型的AD患者MMSE评分低于C/C基因型者(P=0.028)和C/T基因型者(P=0.014).结论 IRP2基因2616C/T多态性与中重度AD相关,而与VD可能无关联;T/T基因型可能是AD患者认知功能损害的危险因子.     

Expression of small heat-shock protein hsp 27 in reactive gliosis in Alzheimer disease and other types of dementia

Immunohistochemical and immunoblotting analysis of brain tissue of Alzheimer's disease (AD) patients showed highly induced expression of the small heat-shock protein hsp 27 in affected cortex. Expression of hsp 27 was present in a large number of proliferating astrocytes. The highest expression was exhibited by degenerative astrocytes in the areas rich in senile plaques. Neurofibrillary tangles, Hirano bodies and some hippocampal neurons were also positive. Expression of hsp 27 increased with the severity of AD-specific morphological changes, and with the duration of dementia. In control brains immunoreaction was restricted to the vessels and to occasional astrocytes in the white matter. Similar patterns of immunoreactivity were present in cases without dementia (Parkinson disease, lacunar state, or focal ischemic necrosis). Patients suffering from other types of dementia (Parkinson/dementia complex, multi-infarct dementia, normal pressure hydrocephalus) showed less expression of hsp 27 in reactive astrocytes than AD, but more than controls. These results indicate that increased expression of hsp 27, especially in astrocytes showing klazmatodendrosis, is associated with AD pathology.Supported by a fellowship of the Royal Netherlands Academy of Arts and Sciences     

Senile dementia of the Alzheimer type in the lundby study

Summary In spite of the great impact of senile dementia of the Alzheimer type (SDAT) on society, far too little is known about its epidemiology. In this study of a total, normal population from a geographically delimited area in Sweden, Lundby, 2612 persons were examined in 1957 by one psychiatrist (Hagnell). In 1972 the same population was reexamined irrespective of domicile. The incidence and risk of contracting SDAT during the 15 years were calculated. No cases of SDAT were diagnosed before the age of 60 years. The lifetime risk was for men 25.7% and for women 26.2%. When only the very severely impaired were taken into account, the figures were 14.5% in men and 14.6% in women.This study has been supported by the following grants: The Bank of Sweden Tercentenary Foundation No. 71/2; The Swedish Medical Research Council Nos. 3474, 4803, 6008, 6881; The Swedish Ministry of Health and Social Affairs, Delegation for Social Research No. 83/64:1–2.The study has been performed with approval of the Ethical Committee of the Lund University Faculty of Medicine and with the permission of the Swedish Data Inspection Board.     

Effects of amyloid precursor protein derivatives andoxidative stress on basal forebrain cholinergic systems inALZHEIMERS disease

The dysfunction and degeneration of cholinergic neuronal circuits in the brain is aprominent feature of Alzheimers disease. Increasing data suggest that age-related oxidative stresscontributes to degenerative changes in basal forebrain cholinergic systems. Experimental studieshave shown that oxidative stress, and membrane lipid peroxidation in particular, can disruptmuscarinic cholinergic signaling by impairing coupling of receptors to GTP-binding proteins.Altered proteolytic processing of the β-amyloid precursor protein (APP) may contributeto impaired cholinergic signaling and neuronal degeneration in at least two ways. First, levels ofcytotoxic forms of amyloid β-peptide (Aβ) are increased ; Aβdamages and kills neurons by inducing membrane lipid peroxidation resulting in impairment ofion-motive ATPases, and glucose and glutamate transporters, thereby rendering neuronsvulnerable to excitotoxicity. The latter actions of Aβ may be mediated by4-hydroxynonenal, an aldehydic product of membrane lipid peroxidation that covalently modifiesand inactivates the various transporter proteins. Subtoxic levels of Aβ can also suppresscholine acetyltransferase levels, and may thereby promote dysfunction of intact cholinergiccircuits. A second way in which altered APP processing may endanger cholinergic neurons is byreducing levels of a secreted form of APP which has been shown to modulate neuronalexcitability, and to protect neurons against excitotoxic, metabolic and oxidative insults. Mutationsin presenilin genes, which are causally linked to many cases of early-onset inherited Alzheimersdisease, may increase vulnerability of cholinergic neurons to apoptosis. The underlying mechanismappears to involve perturbed calcium regulation in the endoplasmic reticulum, which promotesloss of cellular calcium homeostasis, mitochondrial dysfunction and oxyradical production.Knowledge of the cellular and molecular underpinnings of dysfunction and degeneration ofcholinergic circuits is leading to the development of novel preventative and therapeuticapproaches for Alzheimers disease and related disorders.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.