کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5625099 1406269 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Review ArticleAmyloid precursor protein transgenic mouse models and Alzheimer's disease: Understanding the paradigms, limitations, and contributions
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Review ArticleAmyloid precursor protein transgenic mouse models and Alzheimer's disease: Understanding the paradigms, limitations, and contributions
چکیده انگلیسی

Transgenic (Tg) mice that overexpress mutant familial Alzheimer's disease (AD) amyloid precursor protein (APP) genes have contributed to an understanding of dementia pathology, and support the amyloid cascade hypothesis. Although many sophisticated mice APP models exist, none recapitulates AD cellular and behavioral pathology. The morphological resemblance to AD amyloidosis is impressive, but fundamental biophysical and biochemical properties of the APP/Aβ produced in Tg mice differ substantially from those of humans. The greater resilience of Tg mice in the presence of substantial Aβ burdens suggests that levels and forms deleterious to human neurons are not as noxious in these models. Transgenic mice were widely used for testing AD therapeutic agents, and demonstrated promising results. Unfortunately, clinical trials resulted in unforeseen adverse events or negative therapeutic outcomes. The disparity between success and failure is in part attributable to evolutionary divergence between humans and rodents. These observations suggest that the pathogenesis of AD is by far more intricate than can be explained by a straightforward accumulation of Aβ.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Alzheimer's & Dementia - Volume 5, Issue 4, July 2009, Pages 340-347
نویسندگان
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