Daly Timothy, Houot Marion, Barberousse Anouk, Petit Amélie, Epelbaum Stéphane
Sorbonne Université, Science Norms Democracy, Paris, France.
Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.
J Alzheimers Dis Rep. 2021 Aug 6;5(1):637-645. doi: 10.3233/ADR-210030. eCollection 2021.
Therapeutic research into Alzheimer's disease (AD) has been dominated by the amyloid cascade hypothesis (ACH) since the 1990s. However, targeting amyloid in AD patients has not yet resulted in highly significant disease-modifying effects. Furthermore, other promising theories of AD etiology exist.
We sought to directly investigate whether the ACH still dominates the opinions of researchers working on AD and explore the implications of this question for future directions of research.
During 2019, we undertook an international survey promoted with the help of the Alzheimer's Association with questions on theories and treatments of AD. Further efforts to promote a similar study in 2021 did not recruit a significant number of participants.
173 researchers took part in the 2019 survey, 22% of which held "pro-ACH" opinions, tended to have more publications, were more likely to be male, and over 60. Thus, pro-ACH may now be a minority opinion in the field but is nevertheless the hypothesis on which the most clinical trials are based, suggestive of a representation bias. Popular vote of all 173 participants suggested that lifestyle treatments and anti-tau drugs were a source of more therapeutic optimism than anti-amyloid treatments.
We propose a more democratic research structure which increases the likelihood that promising theories are published and funded fairly, promotes a broader scientific view of AD, and reduces the larger community's dependence on a fragile economic model.
自20世纪90年代以来,阿尔茨海默病(AD)的治疗研究一直由淀粉样蛋白级联假说(ACH)主导。然而,针对AD患者的淀粉样蛋白治疗尚未产生高度显著的疾病修饰效果。此外,AD病因还有其他有前景的理论。
我们试图直接调查ACH是否仍然主导着从事AD研究的人员的观点,并探讨这个问题对未来研究方向的影响。
在2019年,我们在阿尔茨海默病协会的帮助下进行了一项国际调查,调查内容涉及AD的理论和治疗方法。2021年进一步推动类似研究的努力并未招募到大量参与者。
173名研究人员参与了2019年的调查,其中22%持有“支持ACH”的观点,他们往往发表的论文更多,更可能为男性,且年龄超过60岁。因此,支持ACH现在可能是该领域的少数观点,但却是大多数临床试验所基于的假说,这暗示了一种代表性偏差。所有173名参与者的民意调查表明,生活方式治疗和抗tau药物比抗淀粉样蛋白治疗更能带来治疗乐观情绪。
我们提出一种更民主的研究结构,这种结构增加了有前景的理论得到公平发表和资助的可能性,促进了对AD更广泛的科学认识,并减少了更大群体对脆弱经济模式的依赖。