Academic Journal
Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment
| العنوان: | Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment |
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| المؤلفون: | Juul-Madsen, Kristian, Parbo, Peter, Ismail, Rola, Ovesen, Peter L., Schmidt, Vanessa, Madsen, Lasse S., Thyrsted, Jacob, Gierl, Sarah, Breum, Mihaela, Larsen, Agnete, Andersen, Morten N., Romero-Ramos, Marina, Holm, Christian K., Andersen, Gregers R., Zhao, Huaying, Schuck, Peter, Nygaard, Jens V., Sutherland, Duncan S., Eskildsen, Simon F., Willnow, Thomas E., Brooks, David J., Vorup-Jensen, Thomas |
| المصدر: | Juul-Madsen , K , Parbo , P , Ismail , R , Ovesen , P L , Schmidt , V , Madsen , L S , Thyrsted , J , Gierl , S , Breum , M , Larsen , A , Andersen , M N , Romero-Ramos , M , Holm , C K , Andersen , G R , Zhao , H , Schuck , P , Nygaard , J V , Sutherland , D S , Eskildsen , S F , Willnow , T E , Brooks , D J & Vorup-Jensen , T 2024 , .... |
| سنة النشر: | 2024 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | Alzheimer Disease/pathology, Amyloid beta-Peptides, Cognitive Dysfunction, Humans, Integrin alphaXbeta2, Monocytes/pathology |
| الوصف: | The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11 C-PiB PET and 18 F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://portal.findresearcher.sdu.dk/da/publications/af61a252-984a-4041-83e3-c53bd9942836 |
| DOI: | 10.1038/s41467-024-45627-y |
| الاتاحة: | https://portal.findresearcher.sdu.dk/da/publications/af61a252-984a-4041-83e3-c53bd9942836 https://doi.org/10.1038/s41467-024-45627-y https://findresearcher.sdu.dk/ws/files/255331788/Open_Access_Version.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.164F3E17 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-45627-y |
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