中华临床医师杂志（电子版） 2010年8月,4卷8期

论　著

阿尔茨海默病与血管性痴呆血浆和脑脊液β淀粉样蛋白肽比较研究

傅燚，肖世富，王涛，林治光，王海红，张雷，陈超

傅燚、肖世富、王涛、林治光、王海红、张雷、陈超，上海交通大学医学院附属精神卫生中心；上海交通大学阿尔茨海默病诊治中心，200030

摘要:目的　探讨β淀粉样蛋白肽Aβ1-40和 Aβ1-42水平在阿尔茨海默病(AD)与血管性痴呆(VD)鉴别诊断中的作用及与认知功能损害的关系。比较AD患者血浆和脑脊液中Aβ1-40 与Aβ1-42含量的异同。方法　收集AD、VD患者各20例，分别测定血浆Aβ1-40、Aβ1-42含量并进行比较。其中10例AD患者同时检测血浆及脑脊液Aβ1-40、Aβ1-42含量并进行比较。采用简明精神状态量表(MMSE)评定认知功能损害。 结果　(1)AD组血浆Aβ1-40含量(69.56±14.15)pg/ml，VD组血浆Aβ1-40含量(78.34±17.24)pg/ml，二者差异无统计学意义(P＞0.05)；AD组血浆Aβ1-42含量(17.61±12.70)pg/ml，VD组血浆Aβ1-42含量(20.23±9.57)pg/ml，二者比较，差异无统计学意义(P＞0.05)。AD组血浆Aβ1-40是Aβ1-42的(5.21±2.64)倍，VD组血浆Aβ1-40是Aβ1-42的(4.56±1.81)倍，两组Aβ1-40/Aβ1-42比值差异无统计学意义(P＞0.05)。 (2)AD组脑脊液Aβ1-40、Aβ1-42含量显著高于血浆，两者比较差异有统计学意义(P＜0.01)。(3)相关性分析显示，AD、VD组血浆Aβ1-40、Aβ1-42含量与认知功能损害、性别、文化程度、病程均无显著相关性(P＞0.05)，AD组Aβ1-40含量与年龄呈显著正相关(r＝0.724，P＝0.000)，VD组Aβ1-42含量与年龄呈显著负相关(r＝－0.606，P＝0.005)，与Aβ1-40之间有显著正相关性(r＝0.567，P＝0.009)。 结论　外周血中Aβ1-40和Aβ1-42水平不能作为临床诊断AD及与VD鉴别的敏感性和特异性指标，血浆中Aβ1-40的检测灵敏度比Aβ1-42更高。血浆Aβ1-40和Aβ1-42水平与发病年龄显著相关。

关键词:阿尔茨海默病；　痴呆，血管性；　淀粉样β蛋白

上海市科学技术委员会重点项目资助(08411951100)；上海市科委自然科学基金项目(10ZR1425800)

A comparative study of plasma and cerebrospinal fluid levels of Aβ1-40 and Aβ1-42 in patients with Alzheimer′s disease and vascular dementia

FU Yi，XIAO Shi-fu，WANG Tao，LIN Zhi-guang，WANG Hai-hong，ZHANG Lei，CHEN Chao.

Shanghai Mental Health Center，Shanghai Jiaotong University School of Medicine，Shanghai 200030，China

Abstract:Objective　To explore the relationship between cognitive function and plasma and cerebrospinal fluid(CSF)levels of amyloid βprotein 1-40(Aβ1-40) and 1-42(Aβ1-42) in patients with Alzheimer′s disease(AD) and vascular dementia(VD)，which was used to diagnosis AD and differential diagnosis of VD.Methods　Twenty patients with AD and 20 patients with VD were recruited.The plasma and CSF Aβ1-40 Aβ1-42 levels were measured in AD group and compared with those in VD group.Cognitive function was assessed by Mini-Mental State Examination(MMSE).Results　The level of plasma Aβ1-40 were (69.56±14.15)pg/ml and (78.34±17.24)pg/ml in AD group and VD group respectively.There were no significant differences between them(P＞0.05).The level of plasma Aβ1-42 were (17.61±12.70)pg/ml and (20.23±9.57)pg/ml in AD group and VD group respectively.There were also no significant differences between them(P＞0.05).The level of plasma Aβ1-40 divided by Aβ1-42 was (5.21±2.64)and (4.56±1.81)times in AD group and VD group respectively.No significant differences were seen in two groups.In AD group，level of Aβ1-40 and Aβ1-42 in CSF were significantly higher than those in plasma，significant differences were found between CSF and plasma(P＞0.05).Correlated analysis showed that the level of Aβ1-40 was positively correlated with the age in AD group(r＝0.724，P＝0.000)and the level of Aβ1-42 was negatively correlated to the age in VD group(r＝－0.606，P＝0.005)，the level of Aβ1-42 was positively correlated to the level of Aβ1-40 in VD group(r＝0.567，P＝0.009).Conclusions　The levels of plasma Aβ1-40 and Aβ1-42 are not the best biomarker to diagnose AD and distinguish AD from VD through.CSF Aβ1-40 and Aβ1-42 levels could be used to diagnose AD in early stage.There are close relationships between levels of Aβ1-40 and Aβ1-42 and age.

Keywords:Alzheimer′s disease；　Dementia，vascular；　Amyloid beta-protein

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参考文献

[1]　Mattson MP. Pathways towards and away from Alzheimer′s disease.Nature,2004,430(7000)：631-639.[PubMed]
[2]　Smith DG，Cappai R，Barnham KJ.The redox chemistry of the Alzheimer′s disease amyloid beta peptide.Biochim Biophys Acta,2007,1768(8)：1976-1990.[PubMed]
[3]　Bibl M，Mollenhauer B，Lewczuk P，et al.Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias.Mol Psychiatry,2007,12(7)：671-680.[PubMed]
[4]　Mollenhauer B，Cullen V，Kahn I，et al.Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration.Exp Neurol,2008,213(2)：315-325.[PubMed]
[5]　Selkoe DJ.Amyloid beta-peptide is produced by cultured cells during nomal metabolism：a reprise.J Alzheimers Dis,2006,9(3 Suppl)：163-168.[PubMed]
[6]　Holmes C， Boche D，Wilkinson D，et al.Long-term effects of Abeta42 immunisation in Alzheimer′s disease：follow-up of a randomised，placebo-controlled phase I trial.Lancet,2008,372(9634)：216-223.[PubMed]
[7]　Kim HD， Jin JJ， Maxwell JA，et al.Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer′s disease.Immunol Lett,2007,112(1)：30-38.[PubMed]
[8]　Wati H， Kawarabayashi T， Matsubara E，et al.Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer′s disease.Brain Pathol,2009,19(1)：48-57.[PubMed]
[9]　薛海波，张明园.阿尔茨海默病的脑脊液标志：总Tau蛋白，磷酸化Tau蛋白和Aβ42.国际精神病学杂志，2006,33(1)：19-24.
[10]　Chatterjee S，Neill R，Shupp JW，et al.Identification of staphylococcal enterotoxin B domains involved in binding to cultured human kidney proximal tubular cells：imparting proliferation and death.Exp Biol Med(Maywood),2007,232(9)：1142-1151.[PubMed]
[11]　Blennow K，De Meyer G，Hansson O，et al.Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer′s disease：a multicenter assessment.J Nutr Health Aging,2009,13(3)：205-208.[PubMed]
[12]　Okereke OI，Xia W，Irizarry MC，et al.Performance characteristics of plasma amyloid-beta 40 and 42 assays.J Alzheimers Dis,2009,16(2)：277-285.[PubMed]
[13]　Verwey NA，Veerhuis R，Twaalfhoven HA，et al.Quantification of amyloid-beta 40 in cerebrospinal fluid.J Immunol Methods,2009,348(1/2)：57-66.[PubMed]
[14]　万毅，金丸和富，山之内博.同时测定脑脊液中Tau蛋白和Aβ1-42含量对诊断阿尔茨海默病的意义.中国神经科学杂志，2003,19(1)：41-44.
[15]　Hansson O，Buchhave P，Zetterberg H，et al.Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer′s disease.Neurobiol Aging,2009,30(2)：165-173.[PubMed]
[16]　Funke SA，Birkmann E，Willbold D.Detection of Amyloid-beta aggregates in body fluids：a suitable method for early diagnosis of Alzheimer′s disease？ Curr Alzheimer Res,2009,6(3)：285-289.[PubMed]
(编辑：戚红丹 收稿日期：2010-01-15)