دورية أكاديمية
The blood clotting Factor XIIIa forms unique complexes with amyloid-beta (Aβ) and colocalizes with deposited Aβ in cerebral amyloid angiopathy.
| العنوان: | The blood clotting Factor XIIIa forms unique complexes with amyloid-beta (Aβ) and colocalizes with deposited Aβ in cerebral amyloid angiopathy. |
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| المؤلفون: | de Jager M; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands., Boot MV; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands., Bol JG; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands., Brevé JJ; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands., Jongenelen CA; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands., Drukarch B; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands., Wilhelmus MM; Department of Anatomy and Neurosciences, Cellular Neuropharmacology Section, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. |
| المصدر: | Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2016 Apr; Vol. 42 (3), pp. 255-72. Date of Electronic Publication: 2015 May 30. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 7609829 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2990 (Electronic) Linking ISSN: 03051846 NLM ISO Abbreviation: Neuropathol Appl Neurobiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, Blackwell Scientific Publications. |
| مواضيع طبية MeSH: | Alzheimer Disease/*metabolism , Amyloid beta-Peptides/*metabolism , Cerebral Amyloid Angiopathy/*metabolism , Factor XIIIa/*metabolism, Aged ; Aged, 80 and over ; Alzheimer Disease/pathology ; Autopsy ; Blotting, Western ; Brain/metabolism ; Brain/pathology ; Cerebral Amyloid Angiopathy/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Surface Plasmon Resonance |
| مستخلص: | Aims: Cerebral amyloid angiopathy (CAA) is a key pathological hallmark of Alzheimer's disease (AD) characterized by accumulation of amyloid-beta (Aβ) protein in blood vessel walls. CAA impairs vessel functioning, affects blood brain barrier integrity and accelerates cognitive decline of AD patients. Unfortunately, mechanisms underlying Aβ deposition in the vessel wall remain largely unknown. Factor XIIIa (FXIIIa) is a blood-derived transglutaminase crucial in blood coagulation by cross-linking fibrin molecules. Evidence is mounting that blood-derived factors are present in CAA and may play a role in protein deposition in the vessel wall. We therefore investigated whether FXIIIa is present in CAA and if FXIIIa cross-link activity affects Aβ aggregation. Methods: Using immunohistochemistry, we investigated the distribution of FXIIIa, its activator thrombin and in situ FXIIIa activity in CAA in post-mortem AD tissue. We used surface plasmon resonance and Western blot analysis to study binding of FXIIIa to Aβ and the formation of FXIIIa-Aβ complexes, respectively. In addition, we studied cytotoxicity of FXIIIa-Aβ complexes to cerebrovascular cells. Results: FXIIIa, thrombin and in situ FXIIIa activity colocalize with the Aβ deposition in CAA. Furthermore, FXIIIa binds to Aβ with a higher binding affinity for Aβ1-42 compared with Aβ1-40 . Moreover, highly stable FXIIIa-Aβ complexes are formed independently of FXIIIa cross-linking activity that protected cerebrovascular cells from Aβ-induced toxicity in vitro. Conclusions: Our data showed that FXIIIa colocalizes with Aβ in CAA and that FXIIIa forms unique protein complexes with Aβ that might play an important role in Aβ deposition and persistence in the vessel wall. (© 2015 British Neuropathological Society.) |
| فهرسة مساهمة: | Keywords: Alzheimer's disease; Aβ oligomerization; Factor XIIIa; cerebral amyloid angiopathy; tissue transglutaminase |
| المشرفين على المادة: | 0 (Amyloid beta-Peptides) EC 2.3.2.13 (Factor XIIIa) |
| تواريخ الأحداث: | Date Created: 20150415 Date Completed: 20170110 Latest Revision: 20170111 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/nan.12244 |
| PMID: | 25871449 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-2990 |
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| DOI: | 10.1111/nan.12244 |