کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3070160 1580712 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease
چکیده انگلیسی

Human genetics link Alzheimer's disease pathogenesis to excessive accumulation of amyloid-β (Aβ) in brain, but the symptoms do not correlate with senile plaque burden. Since soluble Aβ aggregates can cause synaptic dysfunctions and memory deficits, these species could contribute to neuronal dysfunction and dementia. Here we explored selective targeting of large soluble aggregates, Aβ protofibrils, as a new immunotherapeutic strategy. The highly protofibril-selective monoclonal antibody mAb158 inhibited in vitro fibril formation and protected cells from Aβ protofibril-induced toxicity. When the mAb158 antibody was administered for 4 months to plaque-bearing transgenic mice with both the Arctic and Swedish mutations (tg-ArcSwe), Aβ protofibril levels were lowered while measures of insoluble Aβ were unaffected. In contrast, when treatment began before the appearance of senile plaques, amyloid deposition was prevented and Aβ protofibril levels diminished. Therapeutic intervention with mAb158 was however not proven functionally beneficial, since place learning depended neither on treatment nor transgenicity. Our findings suggest that Aβ protofibrils can be selectively cleared with immunotherapy in an animal model that display highly insoluble Aβ deposits, similar to those of Alzheimer's disease brain.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 36, Issue 3, December 2009, Pages 425–434
نویسندگان
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