{"title":"Reduced protein solubility - cause or consequence in amyloid disease?","authors":"Max Lindberg, Jing Hu, Emma Sparr, Sara Linse","doi":"10.1017/qrd.2024.12","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e8"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894405/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"QRB Discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1017/qrd.2024.12","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
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.