Toward clinical application of novel serum peptide biomarkers for dementia with Lewy bodies

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Kurokawa Manae 聖マリアンナ医科大学, 医学研究科, 教授 (90301598)
• Research Collaborator: KATO Tomohiro ; HASEGAWA Yasuhiro ; HORI Koji ; NAGAI Kohei ; SATO Toshiyuki ; SATO Masaaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: レビー小体型認知症 / 血清ペプチド / バイオマーカー / 質量分析 / 内部標準

Outline of Final Research Achievements

Serum peptides which are components of novel biomarker candidates for dementia with Lewy bodies(DLB) were identified and quantified, and their effects on neural cells were examined. One of the peptides, peak of which was at 4090 m/z, was identified as a fragment of a coagulation factor. We prepared internal control peptides labeled with stable isotopes and quantified the peptides, peaks of which were at 1737 m/z, 2898 m/z, 4052 m/z, and 4090 m/z, by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). High linearity was obtained in all the peptide quantification in the range of less than 20 pmol/μL (R2>0.96). Thus, it was suggested that the peptides are accurately quantified by MALDI-TOF/MS using internal standard peptides. Furthermore, those peptides affected cytokine profiles of human hippocampal cells, which indicates that the peptides may be associated with the pathophysiology of DLB and would be a therapeutic target for the disease.

Free Research Field

ペプチドミクス

Academic Significance and Societal Importance of the Research Achievements

DLB/nonDLB-4P及びDLB/nonDLB-2Pモデルを構成するペプチドを全て同定し定量系が構築されれば、DLBを血液検査で診断することが可能となり、早期発見や治療の有効性の判断に簡便に用いることが出来る可能性が高い。アルツハイマー型認知症との鑑別診断も可能となる。また、上記ペプチドは神経細胞の機能を変化させることよりDLBの病態への関連が考えられ、これらペプチドの生成過程を調整することによりDLBの病態を改善出来る可能性がある。