2023-09-12 パシフィック・ノースウェスト国立研究所(PNNL)
◆この研究により、APOEの異なる形態が認知症のリスクに影響を与える可能性が明らかになりました。しかし、その具体的な作用機序は不明です。今後の研究で、リポプロテインと神経疾患の関連性をさらに解明し、治療対象を特定する手がかりを見つけることが期待されています。
<関連情報>
- https://www.pnnl.gov/news-media/researchers-create-new-window-leading-genetic-cause-alzheimers
- https://www.science.org/doi/10.1126/sciadv.adi5571
ヒト脳脊髄液には、中枢神経系の健康に関与するタンパク質に富む多様なリポタンパク質亜種が含まれている Human cerebrospinal fluid contains diverse lipoprotein subspecies enriched in proteins implicated in central nervous system health
Nathaniel J. Merrill ,W. Sean Davidson ,Yi He ,Ivo Díaz Ludovico ,Snigdha Sarkar ,Madelyn R. Berger,Jason E. McDermott ,Linda J. Van Eldik ,Donna M. Wilcock ,Matthew E. Monroe ,Jennifer E. Kyle,Kimberley D. Bruce,Jay W. Heinecke,Tomas Vaisar ,Jacob Raber,Joseph F. Quinn ,and John T. Melchior
Science Advances Published:30 Aug 2023
DOI:https://doi.org/10.1126/sciadv.adi5571
Abstract
Lipoproteins in cerebrospinal fluid (CSF) of the central nervous system (CNS) resemble plasma high-density lipoproteins (HDLs), which are a compositionally and structurally diverse spectrum of nanoparticles with pleiotropic functionality. Whether CSF lipoproteins (CSF-Lps) exhibit similar heterogeneity is poorly understood because they are present at 100-fold lower concentrations than plasma HDL. To investigate the diversity of CSF-Lps, we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF. We identified 10 distinctly sized populations of CSF-Lps, most of which were larger than plasma HDL. Mass spectrometric analysis identified 303 proteins across the populations, over half of which have not been reported in plasma HDL. Computational analysis revealed that CSF-Lps are enriched in proteins important for wound healing, inflammation, immune response, and both neuron generation and development. Network analysis indicated that different subpopulations of CSF-Lps contain unique combinations of these proteins. Our study demonstrates that CSF-Lp subspecies likely exist that contain compositional signatures related to CNS health.
