Microglia Gravitate toward Amyloid Plaques Surrounded by Externalized Phosphatidylserine via TREM2.

Autor: Park JC; Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Department of Metabiohealth, Sungkyunkwan University, Suwon, 16419, Republic of Korea., Han JW; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Lee W; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.; Genome Medicine Institute, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea., Kim J; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Lee SE; Department of Physiology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.; BK21 FOUR Biomedical Science Program, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.; UK Dementia Research Institute, Institute of Neurology, University College London, Gower Street, London, WC1E 6BT, UK.; Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, 03080, Republic of Korea., Lee D; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Choi H; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Han J; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Kang YJ; Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea., Diep YN; Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea., Cho H; Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea., Kang R; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Department of Metabiohealth, Sungkyunkwan University, Suwon, 16419, Republic of Korea., Yu WJ; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.; Department of Metabiohealth, Sungkyunkwan University, Suwon, 16419, Republic of Korea., Lee J; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Choi M; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea., Im SW; Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Gangwon, Seoul, 24341, Republic of Korea., Kim JI; Genome Medicine Institute, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea.; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.; Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea.; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea., Mook-Jung I; Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.; Convergence Dementia Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Sep; Vol. 11 (34), pp. e2400064. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1002/advs.202400064
Abstrakt: Microglia play a crucial role in synaptic elimination by engulfing dystrophic neurons via triggering receptors expressed on myeloid cells 2 (TREM2). They are also involved in the clearance of beta-amyloid (Aβ) plaques in Alzheimer's disease (AD); nonetheless, the driving force behind TREM2-mediated phagocytosis of beta-amyloid (Aβ) plaques remains unknown. Here, using advanced 2D/3D/4D co-culture systems with loss-of-function mutations in TREM2 (a frameshift mutation engineered in exon 2) brain organoids/microglia/assembloids, it is identified that the clearance of Aβ via TREM2 is accelerated by externalized phosphatidylserine (ePtdSer) generated from dystrophic neurons surrounding the Aβ plaques. Moreover, it is investigated whether microglia from both sporadic (CRISPR-Cas9-based APOE4 lines) and familial (APP NL-G-F /MAPT double knock-in mice) AD models show reduced levels of TREM2 and lack of phagocytic activity toward ePtdSer-positive Aβ plaques. Herein new insight is provided into TREM2-dependent microglial phagocytosis of Aβ plaques in the context of the presence of ePtdSer during AD progression.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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