如何看待被引用 2300 多次的阿尔茨海默症「淀粉样蛋白」假说奠基性论文涉嫌造假？
北京时间7月22日凌晨， _Science_ 发表了一篇历时6个月的调查报告，指称美国明尼苏达大学神经学家Sylvain
Lesné发表的20多篇论文中可能存在学术不端行为，其中就包括2006年在 _Nature_ 发表的，阿尔茨海默症“淀粉样蛋白”假说领域的奠基性论文。

可能误导了全世界的阿尔茨海默病研究长达16年

大家如何看待？这件事会有怎么样的影响？
结论加黑：淀粉样蛋白的假说仍然不能被证伪，被实锤的是淀粉样蛋白的一种亚型”Aβ*56“，它的中文翻译应该是”淀粉样蛋白 β 星56“咱们前因后果细细聊1.支持淀粉样变性假说的依据a. 尸检显示，阿尔茨海默病患者的脑中淀粉样蛋白水平高于认知健全的个体。 Amyloidoligomers had been linked to impaired communication between neurons in vitroand in animals, and autopsies have shown higher levels of the oligomers inpeople with Alzheimer’s than in cognitively sound individuals. b.以淀粉样变性为理论基础的转基因动物模型也表现出阿尔兹海默症的症状。In the mid-1990s, she created a transgenicmouse that churns out human Aβ, which forms plaques in the animal’s brain. Themouse also shows dementia-like symptoms. It became a favored Alzheimer’smodel.2.否定淀粉样变性假说的依据a.针对缓解淀粉样变性的的治疗策略和研发的药物全部失效，一个机构8亿美金16年时间全部打水漂 Stoppingamyloid deposits became the most plausible therapeutic strategy.Yet Aβ stilldominates research and drug development. NIH spent about $1.6 billion onprojects that mention amyloids in this fiscal year, about half its overallAlzheimer’s funding. b.淀粉样变性的逆否命题，不能被证明伪（致命缺陷），即当时无法证明Aβ蛋白可以直接导致认知减退But no onehad proved that any one of the many known oligomers directly caused cognitivedecline.2006年，在阿尔兹海默症发现100周年的时间点，各位科研大佬争利用自己的假说取科研经费获取学术资源的时间点，一位被研究所雇来的博士生，年轻的科学家，Lesné，带着Aβ*56来了。The 2006 paper’s first author, sometimes credited as the discoverer of Aβ*56,was Lesné, a young scientist Ashe had hired straight out of a Ph.D. program atthe University of Caen Normandy in France.他成功证明了，Aβ*56可以使健康小鼠表现出阿尔兹海默症的症状。Thegroup isolated Aβ*56 and injected it into young rats. The rats’ capacity torecall simple, previously learned information—such as the location of a hiddenplatform in amaze—plummeted.即他成功证伪淀粉样变性的逆否命题，也就证明了淀粉样变性的真实性，为他和他代表的假说赢取巨额的科研经费。Since then,annual NIH support for studies labeled “amyloid, oligomer, and Alzheimer’s”has risen from near zero to $287 million in 2021. Lesné and Ashe helped sparkthat explosion, expertssay.那么他哪里造假了呢造假的地方在于Aβ*56在小鼠和人类体内分离不出来，即虽然Aβ*56可以导致动物阿尔兹海默症的症状，但是他并不是人体自然病程的产物。“Inscience, once you publish your data, if it’s not readily replicated, thenthere is real concern that it’s not correct or true. There’s precious littleclearcut evidence that Aβ*56 exists, or if it exists, correlates in areproducible fashion with features of Alzheimer’s—even in animalmodels.”目前，争议的主人Lesné博士及其研究受益者仍认为，分离不出来是Aβ*56结构不稳定，无关学术行为不端。Such oligomers arenotoriously unstable, converting to other oligomer types spontaneously.这次造假，使阿尔兹海默症研究领域退回到16年前，学术上再次分为神经免疫假说、炎症假说和淀粉样蛋白变性假说。没有可以证伪的学说，意味着整个领域还处于盲人摸象的状态。