Physiologic origins of age-related β-amyloid deposition
Physiologic origins of age-related β-amyloid deposition
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DOI：
10.1159/000113685
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发表时间：
2008-01-01
影响因子：
3
通讯作者：
Beach, Thomas G.
中科院分区：
文献类型：
--
作者：
Beach, Thomas G.
背景：脑β-淀粉样蛋白（A β）沉积是人类和许多其他哺乳动物衰老的一种非常常见的伴随物。我们假设衰老的正常生理变化导致A β沉积。目的：在年轻的成年家兔中诱导三种正常的生理老化变化，以确定它们对脑A β浓度和沉积的影响。这三种变化是皮质胆碱能神经传入阻滞、高胆固醇血症和雌激素剥夺。方法：侧脑室注射免疫毒素，阻断皮层胆碱能神经传入。用2%胆固醇饮食诱导高胆固醇血症。雌激素剥夺模型与卵巢切除术。结果如下：皮质胆碱能去传入导致皮质A β（42）浓度和脑血管A β沉积增加8倍。高胆固醇血症使皮质A β（42）增加4.6倍，而卵巢切除术使皮质A β（42）增加1.6倍。结论：正常衰老的至少三种生理变化可能是年龄相关的脑A β积累和阿尔茨海默病的基础。版权所有（c）2008 S. Karger AG，巴塞尔。
Background: Brain beta-amyloid (A beta) deposition is an extremely common accompaniment of aging in humans and many other mammalian species. We hypothesized that normal physiological changes of aging cause A beta deposition. Objective: Three normal physiological aging changes were induced in young adult rabbits to determine their effects on brain A beta concentrations and deposition. The three changes were cortical cholinergic deafferentation, hypercholesterolemia and estrogen deprivation. Methods: Cortical cholinergic deafferentation was achieved through intracerebroventricular immunotoxin injection. Hypercholesterolemia was induced with a 2% cholesterol diet. Estrogen deprivation was modeled with ovariectomy. Results: Cortical cholinergic deafferentation resulted in an 8-fold increase in cortical A beta(42) concentrations and cerebovascular A beta deposition. Hypercholesterolemia increased cortical A beta(42) 4.6-fold while ovariectomy increased cortical A beta(42) 1.6-fold. Conclusion: At least three physiological changes of normal aging may underlie age-related brain A beta accumulation and Alzheimer's disease. Copyright (c) 2008 S. Karger AG, Basel.