Lindberg Max, Hu Jing, Sparr Emma, Linse Sara
Biochemistry and Structural Biology, Lund University, Lund, Sweden.
Division for Physical Chemistry, Lund University, Lund, Sweden.
QRB Discov. 2025 Feb 17;6:e8. doi: 10.1017/qrd.2024.12. eCollection 2025.
In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propose a series of possible physicochemical explanations for these observations. These include a reduced solubility, a reduced apparent solubility, as well as a long-lived metastable state manifested in healthy individuals as a free concentration of Aβ42 in the solution phase above the solubility limit. For each scenario, we discuss whether it is most likely a cause or a consequence of the observed protein deposition in the disease.
从这个角度来看，我们提出这样一个问题：在淀粉样变性疾病中，特定蛋白质明显较低的溶解度是此类疾病中蛋白质沉积的原因还是结果。我们聚焦于阿尔茨海默病，首先回顾脑脊液中淀粉样β肽（Aβ42）测量浓度与疾病相关降低的实验证据。我们针对这些观察结果提出了一系列可能的物理化学解释。这些解释包括溶解度降低、表观溶解度降低，以及在健康个体中表现为溶液相中Aβ42游离浓度高于溶解度极限的长寿命亚稳态。对于每种情况，我们讨论它最有可能是疾病中观察到的蛋白质沉积的原因还是结果。
