کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6450953 1416155 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ImmunoPEGliposome-mediated reduction of blood and brain amyloid levels in a mouse model of Alzheimer's disease is restricted to aged animals
ترجمه فارسی عنوان
کاهش سطح خون و آمیلوئید مغزی در یک مدل موش از بیماری آلزایمر، توسط ایمونوفلایپوزوم، محدود به حیوانات سالم است
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی

The accumulation of extracellular amyloid-beta (Aβ) and intracellular neurofibrillary tangles (hyper-phosphorylated Tau) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). Active and passive immunotherapy may limit cerebral Aβ deposition and/or accelerate its clearance. With the aid of a newly characterized monoclonal anti-Aβ antibody we constructed immunoPEGliposomes with high avidity for capturing Aβ in the periphery. The functionality of these vesicles in modulating Aβ uptake by both human brain capillary endothelial hCMEC/D3 cells (suppressing uptake) and THP-1 phagocytes (stimulating uptake) was confirmed in vitro. The multivalent immunoliposomes dramatically reduced circulating and brain levels of Aβ1-40, and particularly Aβ1-42, in “aged” (16 month-old), but not “adult” (10 month-old) APP/PS1 transgenic mice on repeated intraperitoneal administration. Furthermore, the immunoPEGliposome-mediated reduction in amyloidosis correlated with lower levels of glial fibrillary acidic protein (GFAP) and reactive glia (GFAP-positive cells). This treatment also lowered the ratio of phosphorylated Tau to total Tau. The therapeutic efficacy of immunoliposome treatment was superior to free monoclonal antibody administration (at an equivalent antibody dose). The potential mechanisms and significance of age-dependent immunoliposome therapy in AD is discussed.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 112, January 2017, Pages 141-152
نویسندگان
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