Development of blood biomarkers for dementia using antibody-independent isolation of neuron-derived EVs in blood

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23943
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Osaka University
• Principal Investigator: Akamine Shoshin 大阪大学, キャンパスライフ健康支援センター, 特任助教(常勤) (00846222)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 細胞外小胞 / エクソソーム / 認知症

Outline of Final Research Achievements

This research aims to develop a method to separate neuron-derived extracellular vesicles (EVs) from blood based on physical characteristics (i.e., size and density). The size-exclusion chromatography fractionation (SEC) method was used for size-based separation, and the iodixanol density gradient fractionation (IDG) method was used for density-based separation.
The SEC method has the same level of separation performance as the conventional method, but the IDG method has succeeded in achieving higher resolution, making it possible to fractionate EVs in plasma more finely than before. This improvement made it possible that particular neural-derived protein was detected only in specific fractions. This result may indicate that neuron-derived EVs have a "specific density and size" and have different physical properties from other plasma EVs.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

認知症や統合失調症などの精神神経疾患は、脳脊髄液検査や頭部MRI検査などの侵襲性やコストが高い検査のみ実用化されており、血液を用いた身体への負担が低い検査は殆ど存在しない。血液中に微量に存在する神経由来の細胞外小胞（EV）を分離し、その内容物を解析する事で、脳で起きている変化を血液検査で窺い知る事が出来るようになる。神経由来EVの分離には主に抗体を用いたアプローチがなされてきたが、非特異的な結合が大きな課題であった。本研究ではこのような非特異的結合に関する問題を密度・サイズによる分離という別の角度から解決しようと試み、神経由来EVの存在する密度帯・サイズ帯を特定した。