Reimagining Alzheimer's disease--an age-based hypothesis.
Reimagining Alzheimer's disease--an age-based hypothesis.
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重新想象阿尔茨海默氏病 - 基于年龄的假设。
DOI：
10.1523/jneurosci.4521-10.2010
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发表时间：
2010-12-15
期刊：
影响因子：
--
通讯作者：
Herrup K
中科院分区：
文献类型：
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作者：
Herrup K
阿尔茨海默病的历史根源为将该疾病的行为和神经症状与淀粉样蛋白斑块和神经系统缠结的常见相关病理联系起来提供了良好的概念基础。从这些根源中产生了“淀粉样蛋白级联假说”-阿尔茨海默氏症病因学的愿景，激发了对该疾病神经生物学的许多重要见解的发现。尽管取得了这些成功，但生物医学研究人员现在可以获得的大量新数据促使人们对阿尔茨海默氏症的起源进行全面审查，并在这里提供了这样的重新考虑。它始于最广泛接受的发展阿尔茨海默病的风险因素：年龄。然后，对于一个人从正常的年龄适当的认知功能进展到表达全部临床症状的情况，设想了三个关键步骤：1）起始损伤，2）慢性神经炎症反应和3）涉及大多数（如果不是全部）脑细胞类型的不连续细胞状态变化。淀粉样蛋白级联被整合到该序列中，但被重新配置为淀粉样蛋白沉积循环。以这种方式，淀粉样蛋白斑块的病理学被设想为与导致阿尔茨海默病的三个强制性步骤高度相关，但在机制上不同。这一新模式的影响进行了讨论，我们目前的诊断标准和建议提出了扩大我们未来的研究工作。
The historical roots of Alzheimer’s disease provide a sound conceptual basis for linking the behavioral and neurological symptoms of the disease with the frequently associated pathology of amyloid plaques and neurofibrillary tangles. Out of these roots has grown the ‘amyloid cascade hypothesis’ – a vision of the etiology of Alzheimer’s that has spurred the discovery of many important insights into the neurobiology of the disease. Despite these successes, the wealth of new data now available to biomedical researchers urges a full review of the origins of Alzheimer’s and such a reconsideration is offered here. It begins with the most widely accepted risk factor for developing Alzheimer’s disease: age. Then, for an individual to progress from normal age-appropriate cognitive function to a condition where the full palette of clinical symptoms is expressed, three key steps are envisioned: 1) an initiating injury, 2) a chronic neuroinflammatory response and 3) a discontinuous cellular change-of-state involving most, if not all, of the cell types of the brain. The amyloid cascade is integrated into this sequence, but reconfigured as an amyloid deposition cycle. In this way, the pathology of amyloid plaques is envisioned as highly correlated with, but mechanistically distinct from, the three obligatory steps leading to Alzheimer’s disease. The implications of this new model are discussed with respect to our current diagnostic criteria and suggestions are put forward for expanding our future research efforts.