Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias
Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias
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DOI：
10.1038/sj.mp.4001967
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发表时间：
2007-07-01
影响因子：
11
通讯作者：
Wiltfang, J.
中科院分区：
文献类型：
--
作者：
Bibl, M.;Mollenhauer, B.;Wiltfang, J.
用于鉴别诊断三种最常见的退行性痴呆形式（阿尔茨海默病（AD）、路易体痴呆（DLB）和额颞叶痴呆（FTD））的生物标志物目前正在深入研究中，但FTD和DLB的疾病特异性生物标志物仍然缺乏。我们使用定量A β-SDS-PAGE/免疫印迹分析了71例AD、32例DLB和36例FTD患者的303份脑脊液（CSF）样本，并与93例各种其他痴呆（OD）、20例周围神经疾病（PND）对照、25例不伴痴呆的神经退行性疾病（ND）和26例抑郁性认知主诉者（DCC）进行了比较，以确定不同的CSF淀粉样蛋白β（Ab）肽模式。此外，新的电化学发光技术（MSD）用于验证A β 1-38的测量。主要结果指标为AD患者A β 1-42显著降低（P = 7.4 x 10（-19）），最有趣的是FTD患者A β 1-38显著降低（P = 9.6 x 10（-7））。此外，与非痴呆疾病对照组相比，一种最可能代表A β 1-40（A β 1-40（ox））的氧化α-螺旋形式的新型肽显示出DLB的高度显著增加（P = 3.7 x 10（-3））。Ab肽丰度百分比（A β 1-X%）的总体诊断准确性明显优于CSF Ab绝对水平的上级。A β 1-42%和A β 1-38%使得85%或更高的对比能够分别区分AD和FTD与所有其他研究受试者。β 1-40（ox）%在所有其他研究患者中检测DLB的诊断灵敏度和特异性分别为88%和73%。我们发现A β 1-38水平之间存在强相关性，分别通过A β-SDS-PAGE/免疫印迹和MSD测量。CSF A β肽可能反映不同神经退行性过程对A β肽代谢的疾病特异性影响，并代表AD、FTD和DLB的潜在诊断生物标志物。
Biomarkers for differential diagnosis of the three most frequent degenerative forms of dementia, Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementias (FTD), are currently under intensive investigation, but disease-specific biomarkers for FTD and DLB are still lacking. We analyzed 303 cerebrospinal fluid (CSF) samples of 71 AD, 32 DLB and 36 FTD patients in comparison to 93 various other dementias (OD), 20 peripheral neurologic disease (PND) controls, 25 neurodegenerative disorders without dementia (ND) and 26 depressive cognitive complainers (DCC) for distinct CSF amyloid-beta (Ab) peptide patterns, using the quantitative A beta-SDS-PAGE/immunoblot. Additionally, the novel electrochemiluminescence technique (MSD) was used to validate the measures on A beta 1-38. The main outcome measures were a striking decrease of A beta 1-42 in AD ( P = 7.4 x 10(-19)), and most interestingly a pronounced decrease of A beta 1-38 in FTD ( P = 9.6 x 1 0(-7)). Moreover, a novel peptide that most probably represents an oxidized alpha-helical form of A beta 1-40 (A beta 1-40(ox)) displayed a highly significant increase in DLB ( P = 3.7 x 10(-3)) as compared to non-demented disease controls. The overall diagnostic accuracy of percentage Ab peptide abundances (A beta 1-X%) was clearly superior to absolute CSF Ab levels. A beta 1-42% and A beta 1-38% enabled contrasts of 85% or beyond to distinguish AD and FTD, respectively, from all other investigated subjects. A beta 1-40(ox)% yielded a diagnostic sensitivity and specificity of 88 and 73% for the detection of DLB among all other investigated patients. We found a strong correlation between A beta 1-38 levels as measured by the A beta-SDS-PAGE/immunoblot and MSD, respectively. CSF A beta peptides may reflect disease-specific impact of distinct neurodegenerative processes on A beta peptide metabolism and represent a potential diagnostic biomarker for AD, FTD and DLB.