2005 Fiscal Year Final Research Report Summary
Clarification of significance of human brain carboxypeptidase B in cerebrospinal fluid as a diagnostic marker of dementia
| Project/Area Number |
16590860
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Foundation for Biomedical Research and Innovation |
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Principal Investigator |
MATSUMOTO Akira Foundation for Biomedical Research & Innovation, Dept.Brain Disease Pathogenesis Research, Director, 臨床研究情報センター脳疾患病態解析部, 部長 (80181759)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYAMA Shogo Kobe Univ., Graduate School of Medicine, Dept.Gemone Sci., Lecturer, 大学院・医学系研究科, 講師 (80243319)
SAKURAI Takashi Kobe Univ., Graduate School of Medicine, Dept.Gemone Sci., Research Associate, 大学院・医学系研究科, 助手 (50335444)
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| Project Period (FY) |
2004 – 2005
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| Keywords | cerebrospinal fluid / Alzheimer's disease / mild cognitive impairment / early diagnostic marker / mass spectrometry / neurological disease / beta amyloid / carboxypeptidase B |
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| Research Abstract |
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
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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
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