Philosophy Department, Sorbonne Université, Paris, France.
Institut du Cerveau et de la Moelle épinière, ICM, Inserm, U 1127, CNRS, UMR 7225, Sorbonne Université, Inria, Aramis project-team, Inria-APHP collaboration, Paris, France.
J Alzheimers Dis. 2020;74(4):1309-1317. doi: 10.3233/JAD-191321.
The amyloid cascade hypothesis (ACH) has dominated contemporary biomedical research into Alzheimer's disease (AD) since the 1990 s but still lacks definitive confirmation by successful clinical trials of anti-amyloid medicines in human AD. In this uncertain period regarding the centrality of amyloid-β (Aβ) in AD pathophysiology, and with the community apparently divided about the ACH's validity, we used citation practices as a proxy for measuring how researchers have invested their belief in the hypothesis between 1992 and 2019. We sampled 445 articles citing Hardy & Higgins (1992, "HH92") and classified the polarity of their HH92 citation according to Greenberg (2009)'s citation taxonomy of positive, neutral, and negative citations, and then tested four hypotheses. We identified two major attitudes towards HH92: a majority (62%) of neutral attitudes with consistent properties across the time period, and a positive attitude (35%), tending to cite HH92 earlier on within the bibliography as time went by, tending to take HH92 as an established authority. Despite the majority of neutral HH92 citations, there was a positive majority of attitudes toward different versions of the ACH and anti-amyloid therapeutic strategies (65%), suggesting that the ACH has been dominant and has undergone significant refinement since 1992. Finally, of those 110 original articles within the sample also testing the ACH empirically, an overwhelming majority (89%) returned a pro-ACH test result, suggesting that the ACH's central claim is reproducible. Further studies will quantify the extent to which results from different methods within such original studies convergence to provide a robust conclusion vis-à-vis Aβ's pathogenicity in AD.
淀粉样蛋白级联假说（ACH）自 20 世纪 90 年代以来一直主导着阿尔茨海默病（AD）的当代生物医学研究，但在 AD 患者中成功进行抗淀粉样蛋白药物的临床试验仍然缺乏明确的确认。在 AD 病理生理学中淀粉样蛋白-β（Aβ）的核心地位不确定的时期，并且社区显然对 ACH 的有效性存在分歧，我们使用引用实践作为衡量研究人员在 1992 年至 2019 年间对该假说的信任程度的指标。我们对引用了 Hardy 和 Higgins（1992 年，“HH92”）的 445 篇文章进行了抽样，并根据 Greenberg（2009 年）的引用分类法对其 HH92 引用的极性进行了分类，该分类法将引用分为积极、中性和消极三种，然后测试了四个假设。我们确定了对 HH92 的两种主要态度：大多数（62%）持中性态度，且在整个时间段内具有一致的特性，以及积极的态度（35%），随着时间的推移，在参考文献中更早地引用 HH92，并倾向于将 HH92 视为既定权威。尽管大多数 HH92 引用持中立态度，但对 ACH 和抗淀粉样蛋白治疗策略的不同版本持积极态度的人占多数（65%），这表明 ACH 自 1992 年以来一直占据主导地位，并经历了重大改进。最后，在样本中 110 篇测试 ACH 的原始文章中，绝大多数（89%）返回了支持 ACH 的测试结果，这表明 ACH 的核心主张是可复制的。进一步的研究将量化这些原始研究中不同方法的结果在多大程度上收敛，以提供关于 Aβ 在 AD 中的致病性的可靠结论。
