Bishop Glenda M, Robinson Stephen R
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Neurobiol Aging. 2002 Nov-Dec;23(6):1101-5. doi: 10.1016/s0197-4580(02)00050-7.
The 'amyloid hypothesis' has guided research into Alzheimer's disease (AD) for more than a decade. A detailed review of the relevant data led us to conclude that some data, particularly those from transgenic mice, are inconsistent with the predictions of the amyloid hypothesis. Instead, most data are consistent with the notion that amyloid-beta (Abeta) peptide is neuroprotective. The majority of commentators agreed with our analysis but some were unwilling to abandon the amyloid hypothesis until the outcome of anti-Abeta therapeutic trials puts the matter beyond debate. All acknowledged that we had highlighted flaws in the amyloid hypothesis which must be addressed. To stimulate a critical reappraisal of the amyloid hypothesis we have proposed the 'bioflocculant hypothesis' which posits that Abeta serves to bind neurotoxic solutes (pathogens, proteins and metal ions) so that they can be phagocytosed and prevented from causing further damage. The hypothesis makes clear predictions that are readily falsifiable, and it has already gained credibility by predicting the recent negative outcome of Abeta vaccination trials in humans.
“淀粉样蛋白假说”已经指导了对阿尔茨海默病（AD）的研究长达十多年。对相关数据的详细审查使我们得出结论，一些数据，尤其是来自转基因小鼠的数据，与淀粉样蛋白假说的预测不一致。相反，大多数数据与β-淀粉样蛋白（Aβ）肽具有神经保护作用这一观点一致。大多数评论家同意我们的分析，但有些人不愿意放弃淀粉样蛋白假说，直到抗Aβ治疗试验的结果使这一问题无可争议。所有人都承认我们已经突出了淀粉样蛋白假说中必须解决的缺陷。为了激发对淀粉样蛋白假说的批判性重新评估，我们提出了“生物絮凝剂假说”，该假说认为Aβ起到结合神经毒性溶质（病原体、蛋白质和金属离子）的作用，以便它们能够被吞噬并防止造成进一步损害。该假说做出了易于证伪的明确预测，并且通过预测近期人类Aβ疫苗试验的负面结果已经获得了可信度。
