دورية أكاديمية
أعرض في EDS

Elevating microglia TREM2 reduces amyloid seeding and suppresses disease-associated microglia.

التفاصيل البيبلوغرافية
العنوان: Elevating microglia TREM2 reduces amyloid seeding and suppresses disease-associated microglia.
المؤلفون: Zhao N; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Qiao W; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Li F; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Ren Y; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL., Zheng J; Department of Neurology, Mayo Clinic, Rochester, MN.; Neuroscience Graduate Program, Mayo Clinic, Jacksonville, FL., Martens YA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Wang X; Department of Biology, University of North Dakota, Grand Forks, ND., Li L; Department of Biology, University of North Dakota, Grand Forks, ND., Liu CC; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Chen K; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Zhu Y; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Ikezu TC; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Li Z; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Meneses AD; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Jin Y; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Knight JA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Chen Y; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Bastea L; Department of Cancer Biology, Mayo Clinic, Jacksonville, FL., Linares C; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Sonustun B; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Job L; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Smith ML; Department of Neuroscience, Mayo Clinic, Jacksonville, FL., Xie M; Department of Neurology, Mayo Clinic, Rochester, MN.; Neuroscience Graduate Program, Mayo Clinic, Jacksonville, FL., Liu YU; Department of Neurology, Mayo Clinic, Rochester, MN., Umpierre AD; Department of Neurology, Mayo Clinic, Rochester, MN., Haruwaka K; Department of Neurology, Mayo Clinic, Rochester, MN., Quicksall ZS; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL., Storz P; Department of Cancer Biology, Mayo Clinic, Jacksonville, FL., Asmann YW; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL., Wu LJ; Department of Neuroscience, Mayo Clinic, Jacksonville, FL.; Department of Neurology, Mayo Clinic, Rochester, MN.; Neuroscience Graduate Program, Mayo Clinic, Jacksonville, FL., Bu G; Department of Neuroscience, Mayo Clinic, Jacksonville, FL.; Neuroscience Graduate Program, Mayo Clinic, Jacksonville, FL.
المصدر: The Journal of experimental medicine [J Exp Med] 2022 Dec 05; Vol. 219 (12). Date of Electronic Publication: 2022 Sep 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Rockefeller University Press
مواضيع طبية MeSH: Alzheimer Disease*/pathology , Amyloidosis*/pathology, Amyloid/metabolism ; Animals ; Brain/pathology ; Humans ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mice ; Microglia/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism
مستخلص: TREM2 is exclusively expressed by microglia in the brain and is strongly linked to the risk for Alzheimer's disease (AD). As microglial responses modulated by TREM2 are central to AD pathogenesis, enhancing TREM2 signaling has been explored as an AD therapeutic strategy. However, the effective therapeutic window targeting TREM2 is unclear. Here, by using microglia-specific inducible mouse models overexpressing human wild-type TREM2 (TREM2-WT) or R47H risk variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition and neuritic dystrophy only during the early amyloid seeding stage, whereas TREM2-R47H exacerbates amyloid burden during the middle amyloid rapid growth stage. Single-cell RNA sequencing reveals suppressed disease-associated microglia (DAM) signature and reduced DAM population upon TREM2-WT expression in the early stage, whereas upregulated antigen presentation pathway is detected with TREM2-R47H expression in the middle stage. Together, our findings highlight the dynamic effects of TREM2 in modulating AD pathogenesis and emphasize the beneficial effect of enhancing TREM2 function in the early stage of AD development.
(© 2022 Zhao et al.)
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معلومات مُعتمدة: R21 AG064159 United States AG NIA NIH HHS; Florida Department of Health; R37 AG027924 United States AG NIA NIH HHS; RF1 AG046205 United States AG NIA NIH HHS; R01 AG066395 United States AG NIA NIH HHS; RF1 AG056130 United States AG NIA NIH HHS
المشرفين على المادة: 0 (Amyloid)
0 (Membrane Glycoproteins)
0 (Receptors, Immunologic)
0 (TREM2 protein, human)
0 (Trem2 protein, mouse)
تواريخ الأحداث: Date Created: 20220915 Date Completed: 20220919 Latest Revision: 20230317
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9481739
DOI: 10.1084/jem.20212479
PMID: 36107206
قاعدة البيانات: MEDLINE
الوصف
تدمد:1540-9538
DOI:10.1084/jem.20212479