Clarification of significance of human brain carboxypeptidase B in cerebrospinal fluid as a diagnostic marker of dementia

阐明脑脊液中人脑羧肽酶 B 作为痴呆症诊断标志物的意义

• 批准号: 16590860
• 负责人: MATSUMOTO Akira
• 金额: $ 2.3万
• 依托单位: Foundation for Biomedical Research and Innovation
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590860/
• 关键词: cerebrospinal fluid; Alzheimer's disease; mild cognitive impairment; early diagnostic marker; mass spectrometry; neurological disease; beta amyloid; carboxypeptidase B; カルボキシペプチダーゼB; ヒト脳型カルボキシペプチダーゼB; 臨床情報データベース; 髄液

Human brain carboxypeptidase B (HBCPB) exhibits unique characteristics as a candidate marker protein for Alzheimer's disease (AD) ; its prominent expression in the hippocampus which plays significant role in memory and recognition, its in vitro dissociation activity for synthetic beta-amyloid oligomer which inhibits long-term potentiation, its physiological expression in cerebrospinal fluid (CSF), and declined expression in the hippocampus of sporadic AD brains. To explore diagnostic significance of HBCPB expression in CSF, both qualitative and quantitative analyses using mass spectrometry were performed for HBCPB peptides and an array of C-terminally truncated beta-amyloid peptides. The analyses together with clinical informations such as clinical evaluation laboratory examination and image information, statistical study in terms of early diagnostic marker is now being carried out.In the fiscal years of 2004 and 2005, 66 and 31 cases, respectively, were subjected to the study of CSF a … More nd clinical information. Before disclosure limit of clinical information, end of fiscal 2005, all CSF samples were subjected to analysis of HBCPB and bata-amyloid peptides using antibody-assisted mass spectrometric analysis by SELDI TOF-MS platform. According to the results of this analysis, cases were divided into abnormal group (abnormal HBCPB peptide pattern and low A-beta 1-42/A-beta 1-40 ratio), normal group (normal HBCPB peptide pattern and normal A-beta 1-42/A-beta 1-40 ratio) and unclassified group (rest of the above ). After the disclosure of clinical information, selection of HBCPB-derived marker peptide is now under selection and identification, and statistical analysis in terms of AD-diagnostic marker will be under investigation.On the other hand, MCI, which is regarded as the preclinical stage of AD and is actually a crucial research target in the United States, is introduced as sub-category in this study. Since definitive diagnosis of MCI retrospective in nature, to check transition of MCI cases to AD, additional 5-year follow-up study is necessary. Up to now, CSF HBCPB-peptide designated C14EP71-1 and A-beta 1-42/A-beta 1-40 ratio are two candidate markers for early diagnosis of AD/MCI and will be comparatively analyzed. Less

人脑羧肽酶B（HBCP B）是阿尔茨海默病（AD）的候选标志蛋白。其在海马体中的显著表达，其在记忆和识别中起重要作用，其对抑制长时程增强的合成β-淀粉样蛋白寡聚体的体外解离活性，其在脑脊液（CSF）中的生理表达，并且在散发性AD脑的海马中表达下降。为了探索CSF中HBCPB表达的诊断意义，使用质谱法对HBCPB肽和一系列C末端截短的β-淀粉样肽进行了定性和定量分析。结合临床评价、实验室检查、影像学等临床信息，进行早期诊断标志物的统计学研究。2004年和2005年，分别对66例和31例患者进行了CSF分析。 ...更多信息 临床信息。在临床信息披露限制之前，2005财年末，所有CSF样本均通过SELDI TOF-MS平台使用抗体辅助质谱分析进行HBCPB和β-淀粉样肽分析。根据分析结果，将病例分为异常组（HBCPB肽谱异常和A-β 1-42/A-β 1-40比值低）、正常组（HBCPB肽谱正常和A-β 1-42/A-β 1-40比值正常）和未分类组（上述其余）。在临床信息公开后，HBCPB衍生的标志物肽的选择正在筛选和鉴定中，AD诊断标志物的统计分析将在调查中。另一方面，MCI被认为是AD的临床前阶段，实际上是美国的一个重要研究目标，在本研究中被引入作为子类别。由于MCI的明确诊断具有回顾性，为了检查MCI病例向AD的转变，需要进行额外的5年随访研究。到目前为止，CSF HBCPB-肽命名为C14 EP 71 -1和A-β 1-42/A-β 1-40比值是AD/MCI早期诊断的两个候选标志物，并将进行比较分析。少

项目成果

Glycolysis regulates the induction of lactate utilization for synaptic potentials after hypoxia on the granule cell of guinea pig hippocampus.

豚鼠海马颗粒细胞缺氧后，糖酵解调节突触电位的乳酸利用诱导。

• 发表时间: 2004
• 期刊: Neurosci.Res. 50(4)
• 作者: Hinokio Y;Suzuki S;Oka Y.;T.Tanaka et al.
• 通讯作者: T.Tanaka et al.

Learning deficits in N279K tau transgenic mice and an assembly model of tau protein in Molecular Neurobiology of Alzheimer Disease and Related Disorders

阿尔茨海默病及相关疾病的分子神经生物学中 N279K tau 转基因小鼠的学习缺陷和 tau 蛋白的组装模型

• 发表时间: 2004
• 作者: Taizo Taniguchi;Shogo Matsuyama;et al.
• 通讯作者: et al.

Glycolysis regulates the induction of lactate utilization for synaptic potentials after hypoxia in the granule cell of guinea pig hippocampus

• DOI: 10.1016/j.neures.2004.08.008
• 发表时间: 2004-12-01
• 期刊: NEUROSCIENCE RESEARCH
• 影响因子: 2.9
• 作者: Takata, T;Yang, B;Yokono, K
• 通讯作者: Yokono, K

Transgenic mice expressing mutant (N279K) human tau show mutation dependent cognitive deficits without neurofibrillary tangle formation.

表达突变型 (N279K) 人类 tau 蛋白的转基因小鼠表现出突变依赖性认知缺陷，但没有神经原纤维缠结的形成。

• 发表时间: 2005
• 期刊: FEBS Lett. 579
• 作者: Taniguchi;T.他
• 通讯作者: T.他

Spatial learnining of mice lacking a neuron-specific EGF family protein, NELL2,

缺乏神经元特异性 EGF 家族蛋白 NELL2 的小鼠的空间学习

• 发表时间: 2005
• 期刊: J. Pharmacol. Sci. 98(3)
• 作者: ShogoMatsumoto;Nobuyuki Doe;Naoki Kurihara et al.
• 通讯作者: Naoki Kurihara et al.