Evaluation of annexin A5 as a biomarker for Alzheimer's disease and dementia with lewy bodies.

Evaluation of annexin A5 as a biomarker for Alzheimer's disease and dementia with lewy bodies.
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DOI:
10.3389/fnagi.2013.00015
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发表时间:
2013
影响因子:
4.8
通讯作者:
Kokai Y
Kokai Y
中科院分区:
医学2区
文献类型:
--
作者:
Sohma H;Imai S;Takei N;Honda H;Matsumoto K;Utsumi K;Matsuki K;Hashimoto E;Saito T;Kokai Y

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背景:阿尔茨海默病(Alzheimer's disease,AD)与其他类型的痴呆不同之处在于其与淀粉样β肽(amyloid beta peptide,Aβ42)的关系。使用细胞培养模型,我们以前确定膜联蛋白A5,钙离子和磷脂结合蛋白,作为AD生物标志物。AD患者血浆膜联蛋白A5水平显著高于对照组。另一方面,AD已被鉴定为与路易体痴呆(DLB)共享许多临床和病理特征。本研究的目的是检查血浆膜联蛋白A5是否是AD的特异性标志物,与DLB患者的水平进行比较。由于载脂蛋白E(ApoE)基因亚型ε4(ApoE-ε4)已被认为是AD的可能遗传因素,我们还对AD和DLB的ApoE基因型进行了检测和比较。研究方法:采集150例AD患者(年龄77.6 ± 6.5岁)、50例DLB患者(年龄79.4 ± 5.0岁)和279例年龄和性别相当的社区健康老年人(年龄75.6 ± 8.1岁)的血样。所有AD患者均符合NINCDS-ADRDA标准,所有DLB患者均根据最新共识诊断标准诊断为可能DLB。使用针对膜联蛋白A5的单克隆抗体,使用化学发光酶免疫测定(CLEIA)技术(SphereLight测定)进行定量。通过区分PCR扩增基因组DNA产物的Hha 1片段的独特组合进行ApoE的DNA基因分型。结果:AD患者血浆AnnexinA 5水平显著高于健康对照组(P < 0.0001)。DLB患者血浆Annexin A5水平也显著高于对照组(P < 0.0001)。根据血浆膜联蛋白A5浓度的ROC曲线,AD/对照和DLB/对照的平均曲线下面积分别为0.863和0.838。AD组和DLB组ApoE 4携带率和ε4等位基因频率均显著高于对照组,而AD组和DLB组之间无显著性差异。结论:Annexin A5和ApoE 4是AD和DLB的共同标志物。
Background: Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Aβ42). Using a cell culture model we previously identified annexin A5, a Ca2+, and phospholipid binding protein, as an AD biomarker. Plasma level of annexin A5 was significantly higher in AD patients compared to that in a control group. On the other hand, AD has been identified to share a number of clinical and pathological features with Dementia with Lewy bodies (DLB). The present study was done to examine whether or not plasma annexin A5 is a specific marker for AD, when being compared with the levels of DLB patients. As Apolipoprotein E (ApoE) gene subtype ε4 (ApoE-ε4) has been noticed as the probable genetic factor for AD, we also examined and compared ApoE genotype in both AD and DLB. Methods: Blood samples were obtained from 150 patients with AD (aged 77.6 ± 6.5 years), 50 patients of DLB (79.4 ± 5.0) and 279 community-dwelling healthy elderly individuals of comparable age and sex (75.6 ± 8.1). All AD patients met NINCDS-ADRDA criteria and all DLB patients were diagnosed as probable DLB according to the latest consensus diagnostic criteria. Quantification was done using the Chemiluminescent Enzyme Immunoassay (CLEIA) Technique (SphereLight assay) using the monoclonal antibodies against annexin A5. DNA genotyping of ApoE was performed by distinguishing unique combinations of Hha1 fragments of PCR-amplified genomic DNA products. Results: The plasma level of annexin A5 was significantly higher in AD patients than in the healthy individuals (control) (P < 0.0001). The plasma annexin A5 level was also significantly higher in DLB patients than in the control group (P < 0.0001). From the ROC curves with plasma annexin A5 concentrations, the mean areas under the curve were 0.863 and 0.838 for the AD/control and DLB/control, respectively. The rate of ApoE4 carrier status and the frequency of the ε4 allele were significantly higher in AD or DLB than in control and there was no significant difference between AD and DLB. Conclusions: These results suggest that both annexin A5 and ApoE4 are common markers for AD and DLB.
DOI: 10.1126/science.3283935
发表时间: 1988-04-29
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: MAHLEY, RW
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