中晚期阿尔茨海默病与血管性痴呆患者血浆Aβ及tau蛋白水平的比较研究
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摘要
目的:比较中晚期阿尔茨海默病(Alzheimer’sdisease,AD)与血管性痴呆(vascular dementia,VD)患者血浆标志物(Aβ_(40),Aβ_(42)以及t-tau蛋白,p-tau181蛋白)的差异,并对血浆标志物的相关影响因素进行分析。方法:招募住院中晚期AD与VD患者共77例,收集一般资料、临床生化指标,并采用Luminex检测平台分别检测AD与VD患者血浆标志物的含量,采用逐步回归分析分析相关因素。结果:AD患者血浆中Aβ_(40)、Aβ_(42)、t-tau蛋白及p-tau181蛋白含量均小于VD组患者,但差异无显著意义。相关性及逐步回归分析中表明,Aβ与tau蛋白密切相关,同时胰岛素和低密度脂蛋白水平及CDR分级均会影响血浆标志物。结论:血浆中Aβ_(40)、Aβ_(42)、t-tau蛋白及p-tau181蛋白不能用于诊断和鉴别AD与VD,但血浆标志物水平与痴呆炎症程度、低密度脂蛋白和胰岛素水平密切相关,能用于痴呆诊断。
Objective To compare the plasma levels of Aβ_(40), Aβ_(42), t-Tau and p-Tau181 of patients with moderate and severe Alzheimer's disease(AD) and vascular dementia(VD), and analyze potential factors associated with plasma biomarkers. Methods A total of 77 admitted patientswith moderate and severe AD or VD were recruited and their clinical information and biochemical parameters were measured. The plasma biomarkers were detected using LuminexxMAP liquid chip technology. The potentially related factors were analyzed by stepwise regression analysis. Results The plasma level of Aβ_(40), Aβ_(42), t-Tau and p-Tau181 were not significantly different between AD group and VD group, but with lower levels in AD group. Correlation and stepwise regression analysis showed that Aβ is closely related to tau protein, while the levels of insulin and LDL and CDR were corrlated with the plasma biomarkers. Conclusions The levels of insulin and LDL and severity of dementia could affect the plasma biomarkers. The plasma levels of Aβ_(40), Aβ_(42), t-Tau and p-Tau181 may not be the useful biomarkers for the discrimination AD from VD.
Objective To compare the plasma levels of Aβ_(40), Aβ_(42), t-Tau and p-Tau181 of patients with moderate and severe Alzheimer's disease(AD) and vascular dementia(VD), and analyze potential factors associated with plasma biomarkers. Methods A total of 77 admitted patientswith moderate and severe AD or VD were recruited and their clinical information and biochemical parameters were measured. The plasma biomarkers were detected using LuminexxMAP liquid chip technology. The potentially related factors were analyzed by stepwise regression analysis. Results The plasma level of Aβ_(40), Aβ_(42), t-Tau and p-Tau181 were not significantly different between AD group and VD group, but with lower levels in AD group. Correlation and stepwise regression analysis showed that Aβ is closely related to tau protein, while the levels of insulin and LDL and CDR were corrlated with the plasma biomarkers. Conclusions The levels of insulin and LDL and severity of dementia could affect the plasma biomarkers. The plasma levels of Aβ_(40), Aβ_(42), t-Tau and p-Tau181 may not be the useful biomarkers for the discrimination AD from VD.
引文
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[20]韩丽珠,王文静,褚忠海,等.轻度认知障碍患者脑脊液中?-淀粉样蛋白42及磷酸化Tau蛋白的水平检测及意义[J].实用医学杂志,2014(19):3079-3081.
[21]Martinez A.First non-ATP competitive glycogen synthase kinase 3β(GSK-3β)inhibitors:Thiadiazolidinones(TDZD)as potential drugs for the treatment of Alzheimer’s disease[J].J Med Chem,2002,45(6):1292-1299.
[22]耿琳,张云明,李晔,et al.老年痴呆与血浆同型半胱氨酸水平关系的临床研究[J].现代生物医学进展,2012,12(9):1683-1685.
[23]毕胜,王德生,张昱,et al.血管性痴呆患者与其血浆同型半胱氨酸水平的关系[J].中华老年心脑血管病杂志,2000,2(5).
[2]上海市新华医院神经内科上海.A?蛋白在阿尔兹海默病中的损伤机制以及研究进展[J].中国实用神经疾病杂志,2015(1):127-129.
[3]范月丹,张娴,曾乐平,et al.Tau蛋白在阿尔兹海默病治疗中的研究进展[J].现代生物医学进展,2015,15(33):6596-6600.
[4]张雪玲,丁新生,程虹,et al.脑脊液中A?检测对老年期痴呆早期诊断的意义[J].现代中西医结合杂志,2003(8):789-790.
[5]许二赫,武剑,贾建平.血管性痴呆患者血浆中A?及Tau蛋白的检测分析[J].中风与神经疾病杂志,2010,27(5):413-415.
[6]Jia J P,Meng R,Sun Y X,et al.Cerebrospinal fluid tau,Aβ1-42 and inflammatory cytokines in patients with Alzheimer’s disease and vascular dementia[J].Neurosci Lett,2005,383(1-2):12-16.
[7]陈路明,徐斌,严家川.脑脊液?-淀粉样蛋白/磷酸化tau蛋白比值在鉴别诊断阿尔茨海默病与血管性痴呆中的价值[J].现代生物医学进展,2009,9(5):922-924.
[8]Coughlan C M,Breen K C.Factors influencing the processing and function of the amyloid beta precursor protein--a potential therapeutic target in Alzheimer’s disease?[J].Pharmacol Ther NLM,2000,86(2):111-144.
[9]潘名志,杜向东,徐晓文,et al.阿尔茨海默病患者血清Hcy、A?1-42、Tau蛋白水平测定及临床意义[J].中国卫生检验杂志,2013(6):1511-1512.
[10]季娜,郑欣宁,张凤华,et al.血液中A?1-42和P-tau181对阿尔茨海默病临床诊断的应用价值[J].医学与哲学(B),2017(11):42-44+52.
[11]傅燚,肖世富,王涛,等.阿尔茨海默病与血管性痴呆血浆和脑脊液?淀粉样蛋白肽比较研究[J].中华临床医师杂志(电子版),2010,04(8):6-9.
[12]Larson M E,Sylvain E.Lesné.Soluble Aβoligomer production and toxicity[J].J NEUROCHEM,2012,120(s1):15.
[13]Binder,L.I.The distribution of tau in the mammalian central nervous system[J].J Cell Biol,1985,101(4):1371-1378.
[14]Neurofilament protein in cerebrospinal fluid:A marker of white matter changes[J].J NEUROSCI RES,2001,66(3):510-516.
[15]H Hénon,Durieu I,Lucas C,et al.Dementia in stroke[J].Neurology,1996,47(3):852-853.
[16]Krishnan S,Rani P.Evaluation of Selenium,Redox Status and Their Association with Plasma Amyloid/Tau in Alzheimer’s Disease[J].Biol Trace Elem Res,2014,158(2):158-165.
[17]Langa K M,Foster N L,Larson E B.Mixed Dementia:Emerging Concepts and Therapeutic Implications[J].Jama,2004,292(23):2901-2908.
[18]Walter,Jochen.γ-Secretase,Apolipoprotein E and Cellular Cholesterol Metabolism[J].Curr Alzheimer Res,2012,9(2):189-199.
[19]袁树华,高顺宗,刘雪平,et al.胰岛素抵抗大鼠认知功能的变化及其脑组织Alzheimer样病变[J].卒中与神经疾病,2010,17(3):139-143.
[20]韩丽珠,王文静,褚忠海,等.轻度认知障碍患者脑脊液中?-淀粉样蛋白42及磷酸化Tau蛋白的水平检测及意义[J].实用医学杂志,2014(19):3079-3081.
[21]Martinez A.First non-ATP competitive glycogen synthase kinase 3β(GSK-3β)inhibitors:Thiadiazolidinones(TDZD)as potential drugs for the treatment of Alzheimer’s disease[J].J Med Chem,2002,45(6):1292-1299.
[22]耿琳,张云明,李晔,et al.老年痴呆与血浆同型半胱氨酸水平关系的临床研究[J].现代生物医学进展,2012,12(9):1683-1685.
[23]毕胜,王德生,张昱,et al.血管性痴呆患者与其血浆同型半胱氨酸水平的关系[J].中华老年心脑血管病杂志,2000,2(5).