McCaulley Mark E, Grush Kira A
Yampa Valley Medical Associates, Steamboat Springs, CO, USA.
University of Colorado School of Medicine, Aurora, CO, USA.
Int J Alzheimers Dis. 2017;2017:2438901. doi: 10.1155/2017/2438901. Epub 2017 Dec 5.
There is no effective etiologic treatment for Alzheimer's disease, nor is there a prophylactic medication which delays or prevents its onset. The lack of an accurate paradigm is undoubtedly related to the lack of effective means of prophylaxis and treatment. The current paradigm of beta amyloid in Alzheimer's brains causing cognitive dysfunction must be modified. Despite failed clinical trials, research continues into amyloid-oriented treatments. The persistence of the amyloid hypothesis/paradigm is an example of anchoring and representativeness heuristics described by Kahneman and Tversky in their classic 1974 paper. Economic factors also contribute to the persistence of this paradigm. Paradigms impact the scientific process by the following: (1) what is studied; (2) the types of questions that are asked; (3) the structure and nature of the questions; (4) the interpretations of research findings. We review the contribution of inflammation, malfunction of the neurovascular unit, and prion disease to Alzheimer's disease manifestations. Any or all of these are candidates for inclusion into a more accurate, inclusive, and useful new paradigm. By incorporating emerging facts and understanding into a new paradigm, we will enhance our ability to move toward effective prophylaxis and therapy for this tragic disease.
目前尚无针对阿尔茨海默病的有效病因治疗方法，也没有能延缓或预防其发病的预防性药物。缺乏准确的范式无疑与缺乏有效的预防和治疗手段有关。当前关于阿尔茨海默病患者大脑中β淀粉样蛋白导致认知功能障碍的范式必须加以修正。尽管临床试验失败，但针对淀粉样蛋白的治疗研究仍在继续。淀粉样蛋白假说/范式的持续存在是卡尼曼和特沃斯基在其1974年经典论文中所描述的锚定和代表性启发法的一个例子。经济因素也促使这一范式持续存在。范式通过以下方式影响科学进程：（1）研究的内容；（2）所提问题的类型；（3）问题的结构和性质；（4）对研究结果的解释。我们综述了炎症、神经血管单元功能障碍和朊病毒病对阿尔茨海默病表现的影响。这些因素中的任何一个或全部都有可能被纳入一个更准确、更全面且更有用的新范式。通过将新出现的事实和认识纳入新范式，我们将提高针对这种悲惨疾病实现有效预防和治疗的能力。
