Frankfort Suzanne V, van Campen Jos P C M, Tulner Linda R, Beijnen Jos H
Department of Geriatric Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
Curr Clin Pharmacol. 2008 Sep;3(3):144-54. doi: 10.2174/157488408785747665.
By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDI-TOF MS) an amyloid beta (Abeta) profile was shown in cerebrospinal fluid (CSF) of patients with dementia.
To investigate the Abeta-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of Abeta-peptide-peaks in serum and clinical, demographical and genetic variables.
Duplicate profiling of Abeta by an SELDI-TOF MS immunocapture assay was performed in 106 patients, suffering from Alzheimer's Disease or Vascular Dementia and age-matched non-demented control patients. Linear regression analyses were performed to investigate the intensities of four selected Abeta peaks as dependent variables in relation to the independent clinical, demographic or genetic variables.
Abeta37, Abeta38 and Abeta40 were found among additional unidentified Abeta peptides, with the most pronounced Abeta peak at a molecular mass of 7752. This profile partly resembled the CSF profile. The clinical diagnosis was not a predictive independent variable, however ABCB1 genotypes C1236T, G2677T/A, age and creatinine level showed to be related to Abeta peak intensities in multivariate analyses.
We found an Abeta profile in serum that partly resembled the CSF profile in demented patients. Age, creatinine levels, presence of the APOE epsilon4 allele and ABCB1 genotypes (C1236T and G2677T/A) were correlated with the Abeta serum profile. The role of P-gp as an Abeta transporter and the role of ABCB1 genotypes deserves further research. The investigated serum Abeta profile is probably not useful in the diagnosis of dementia.
通过表面增强激光解吸/电离飞行时间质谱(SELDI-TOF MS),在痴呆患者的脑脊液(CSF)中显示出淀粉样β蛋白(Aβ)谱。
用SELDI-TOF MS研究血清中的Aβ谱,评估该谱是否与脑脊液谱相似,并研究血清中Aβ肽峰强度与临床、人口统计学和遗传变量之间的相关性。
对106例患有阿尔茨海默病或血管性痴呆的患者以及年龄匹配的非痴呆对照患者,采用SELDI-TOF MS免疫捕获分析法对Aβ进行重复分析。进行线性回归分析,以研究四个选定的Aβ峰强度作为因变量与独立的临床、人口统计学或遗传变量的关系。
在其他未鉴定的Aβ肽中发现了Aβ37、Aβ38和Aβ40,分子量为7752处的Aβ峰最为明显。该谱部分类似于脑脊液谱。临床诊断不是一个预测性独立变量,然而在多变量分析中,ABCB1基因C1236T、G2677T/A、年龄和肌酐水平与Aβ峰强度相关。
我们在血清中发现了一种Aβ谱,部分类似于痴呆患者的脑脊液谱。年龄、肌酐水平、APOE ε4等位基因的存在以及ABCB1基因型(C1236T和G2677T/A)与血清Aβ谱相关。P-糖蛋白作为Aβ转运体的作用以及ABCB1基因型的作用值得进一步研究。所研究的血清Aβ谱可能对痴呆的诊断无用。