دورية أكاديمية
Evidence for peripheral clearance of cerebral Aβ protein following chronic, active Aβ immunization in PSAPP mice
| العنوان: | Evidence for peripheral clearance of cerebral Aβ protein following chronic, active Aβ immunization in PSAPP mice |
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| المؤلفون: | Cynthia A Lemere, Edward T Spooner, John LaFrancois, Brian Malester, Chica Mori, Jodi F Leverone, Yasuji Matsuoka, Jennie W Taylor, Ronald B DeMattos, David M Holtzman, John D Clements, Dennis J Selkoe, Karen E Duff |
| المصدر: | Neurobiology of Disease, Vol 14, Iss 1, Pp 10-18 (2003) |
| بيانات النشر: | Elsevier, 2003. |
| سنة النشر: | 2003 |
| المجموعة: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| مصطلحات موضوعية: | Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: | Immunization with amyloid-β (Aβ) peptide in mouse models of Alzheimer’s disease has been reported to decrease cerebral Aβ levels and improve behavioral deficits. Several mechanisms have been proposed, including antibody-induced phagocytosis of Aβ by cerebral microglia and increased efflux of Aβ from the brain to the periphery. The latter mechanism was suggested in mice undergoing acute, passive transfer of an Aβ monoclonal antibody. Here, PSAPP transgenic mice were actively immunized by a single intraperitoneal injection of synthetic Aβ followed by chronic intranasal administration of Aβ with the mucosal adjuvant, Escherichia coli heat-labile enterotoxin, LT, twice weekly for 8 weeks. Serum from Aβ-immunized mice had an average of 240 μg/ml of anti-Aβ-specific antibodies; these antibodies had epitope(s) within Aβ1-15 and were of immunoglobulin (Ig) isotypes IgG2b, IgG2a, and IgG1. Immunization led to a 75% decrease in plaque number (P < 0.0001) and a 58% decrease in Aβx–42 levels (P < 0.026) in brain, and gliosis and neuritic dystrophy were diminished. No pathological effects of the immunization were observed in kidney, spleen, or snout. Serum Aβ levels increased 28-fold in immunized mice (53.06 ng/ml) compared to controls (1.87 ng/ml). Most of the Aβ in the serum of the immunized mice was bound to antibodies. We conclude that following active immunization, anti-Aβ antibodies sequester serum Aβ and may increase central nervous system to serum Aβ clearance. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1095-953X 0969-9961 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0969996103000445; https://doaj.org/toc/1095-953X |
| DOI: | 10.1016/S0969-9961(03)00044-5 |
| URL الوصول: | https://doaj.org/article/4f47f1c3bb8b443086efd9bb58489f0a |
| رقم الأكسشن: | edsdoj.4f47f1c3bb8b443086efd9bb58489f0a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 1095953X 09699961 |
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| DOI: | 10.1016/S0969-9961(03)00044-5 |