{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:38:29Z","timestamp":1792715909361,"version":"4.5.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Molecular Biology"],"published-print":{"date-parts":[[2008,3]]},"DOI":"10.1016\/j.jmb.2007.12.079","type":"journal-article","created":{"date-parts":[[2008,1,14]],"date-time":"2008-01-14T12:20:02Z","timestamp":1200313202000},"page":"565-574","source":"Crossref","is-referenced-by-count":51,"title":["Mutations Enhance the Aggregation Propensity of the Alzheimer\u2019s A\u03b2 Peptide"],"prefix":"10.1016","volume":"377","author":[{"given":"Woojin","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Hecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jmb.2007.12.079_bib1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","article-title":"Alzheimer\u2019s disease: genes, proteins, and therapy","volume":"81","author":"Selkoe","year":"2001","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.jmb.2007.12.079_bib2","doi-asserted-by":"crossref","first-page":"10836","DOI":"10.1073\/pnas.90.22.10836","article-title":"\u03b2-Amyloid-(1\u201342) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease","volume":"90","author":"Roher","year":"1993","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2007.12.079_bib3","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1021\/bi00069a001","article-title":"The carboxy terminus of the \u03b2-amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer\u2019s disease","volume":"32","author":"Jarrett","year":"1993","journal-title":"Biochemistry"},{"key":"10.1016\/j.jmb.2007.12.079_bib4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev.biochem.66.1.385","article-title":"Models of amyloid seeding in Alzheimer\u2019s disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins","volume":"66","author":"Harper","year":"1997","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.jmb.2007.12.079_bib5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: the amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"10.1016\/j.jmb.2007.12.079_bib6","doi-asserted-by":"crossref","first-page":"21153","DOI":"10.1074\/jbc.273.33.21153","article-title":"Molecular dissection of domains in mutant presenilin 2 that mediate overproduction of amyloidogenic forms of amyloid \u03b2-peptides","volume":"273","author":"Tomita","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2007.12.079_bib7","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.1074\/jbc.M209252200","article-title":"Familial Alzheimer disease-linked presenilin 1 variants enhanced production of both A\u03b21\u201340 and A\u03b21\u201342 peptides that are only partially sensitive to a potent aspartyl protease transition state inhibitor of \u201c\u03b3-secretase\u201d","volume":"278","author":"Ikeuchi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2007.12.079_bib8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1006\/nbdi.1998.0202","article-title":"Flemish and Dutch mutations in amyloid \u03b2 precursor protein have different effects on amyloid \u03b2 secretion","volume":"5","author":"De Jonghe","year":"1998","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.jmb.2007.12.079_bib9","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1096\/fj.05-5628com","article-title":"Increased BACE1 maturation contributes to the pathogenesis of Alzheimer\u2019s disease in Down syndrome","volume":"20","author":"Sun","year":"2006","journal-title":"FASEB J."},{"key":"10.1016\/j.jmb.2007.12.079_bib10","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.neurobiolaging.2004.02.027","article-title":"A\u03b2 localization in abnormal endosomes: association with earliest A\u03b2 elevations in AD and Down syndrome","volume":"25","author":"Cataldo","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.jmb.2007.12.079_bib11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/00019052-200404000-00003","article-title":"Down syndrome and \u03b2-amyloid deposition","volume":"17","author":"Head","year":"2004","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.jmb.2007.12.079_bib12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nm0196-93","article-title":"Presence of soluble amyloid \u03b2-peptide precedes amyloid plaque formation in Down\u2019s syndrome","volume":"2","author":"Teller","year":"1996","journal-title":"Nat. Med."},{"key":"10.1016\/j.jmb.2007.12.079_bib13","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1073\/pnas.94.4.1550","article-title":"Amyloid precursor protein processing and A\u03b242 deposition in a transgenic mouse model of Alzheimer disease","volume":"94","author":"Johnson-Wood","year":"1997","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2007.12.079_bib14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neuroscience.2004.12.025","article-title":"Intraneural A\u03b2, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer\u2019s disease","volume":"132","author":"Crowther","year":"2005","journal-title":"Neuroscience"},{"key":"10.1016\/j.jmb.2007.12.079_bib15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0197-4580(02)00224-5","article-title":"Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer\u2019s disease model","volume":"24","author":"Link","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.jmb.2007.12.079_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/JBB\/2006\/58406","article-title":"\u03b2-Amyloid degradation and Alzheimer\u2019s disease","volume":"2006","author":"Wang","year":"2006","journal-title":"J. Biomed. Biotechnol."},{"key":"10.1016\/j.jmb.2007.12.079_bib17","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1097\/01.jnen.0000240463.87886.9a","article-title":"Decreased expression and activity of neprilysin in Alzheimer disease are associated with cerebral amyloid angiopathy","volume":"65","author":"Miners","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.jmb.2007.12.079_bib18","doi-asserted-by":"crossref","first-page":"30471","DOI":"10.1074\/jbc.M605827200","article-title":"Regulation of steady-state \u03b2-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme","volume":"281","author":"Eckman","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2007.12.079_bib19","doi-asserted-by":"crossref","first-page":"6027","DOI":"10.1016\/j.febslet.2005.09.054","article-title":"Neprilysin decreases uniformly in Alzheimer\u2019s disease and in normal aging","volume":"579","author":"Russo","year":"2005","journal-title":"FEBS Lett."},{"key":"10.1016\/j.jmb.2007.12.079_bib20","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.nbd.2006.08.003","article-title":"Neuronal neprilysin overexpression is associated with attenuation of A\u03b2-related memory deficit","volume":"24","author":"Poirier","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.jmb.2007.12.079_bib21","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature04533","article-title":"A specific amyloid-\u03b2 protein assembly in the brain impairs memory","volume":"440","author":"Lesne","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.jmb.2007.12.079_bib22","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1523\/JNEUROSCI.4391-04.2005","article-title":"Certain inhibitors of synthetic amyloid \u03b2-peptide (A\u03b2) fibrillogenesis block oligomerization of natural A\u03b2 and thereby rescue long-term potentiation","volume":"25","author":"Walsh","year":"2005","journal-title":"J. Neurosci."},{"key":"10.1016\/j.jmb.2007.12.079_bib23","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid-\u03b2 protein potently inhibit hippocampal long-term potentiation in vivo","volume":"416","author":"Walsh","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.jmb.2007.12.079_bib24","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/S0022-2836(02)00399-6","article-title":"Mutations that reduce aggregation of the Alzheimer\u2019s A\u03b242 peptide: an unbiased search for the sequence determinants of A\u03b2 amyloidogenesis","volume":"319","author":"Wurth","year":"2002","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib25","doi-asserted-by":"crossref","first-page":"15824","DOI":"10.1073\/pnas.0605629103","article-title":"Generic hydrophobic residues are sufficient to promote aggregation of the Alzheimer\u2019s A\u03b242 peptide","volume":"103","author":"Kim","year":"2006","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2007.12.079_bib26","doi-asserted-by":"crossref","first-page":"35069","DOI":"10.1074\/jbc.M505763200","article-title":"Sequence determinants of enhanced amyloidogenicity of Alzheimer A\u03b242 peptide relative to A\u03b240","volume":"280","author":"Kim","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2007.12.079_bib27","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.jmb.2003.11.008","article-title":"Mapping A\u03b2 amyloid fibril secondary structure using scanning proline mutagenesis","volume":"335","author":"Williams","year":"2004","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib28","doi-asserted-by":"crossref","first-page":"52781","DOI":"10.1074\/jbc.M406262200","article-title":"Analysis of the secondary structure of \u03b2-amyloid (A\u03b242) fibrils by systematic proline replacement","volume":"27","author":"Morimoto","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2007.12.079_bib29","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nature01891","article-title":"Rationalization of the effects of mutations on peptide and protein aggregation rates","volume":"424","author":"Chiti","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.jmb.2007.12.079_bib30","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1110\/ps.3150102","article-title":"Charge states rather than propensity for \u03b2-structure determine enhanced fibrillogenesis in wild-type Alzheimer\u2019s \u03b2-amyloid peptide compared to E22Q Dutch mutant","volume":"11","author":"Massi","year":"2002","journal-title":"Protein Sci."},{"key":"10.1016\/j.jmb.2007.12.079_bib31","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/10904","article-title":"Rapid protein-folding assay using green fluorescent protein","volume":"17","author":"Waldo","year":"1999","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jmb.2007.12.079_bib32","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1021\/cb600135w","article-title":"A high-throughput screen for compounds that inhibit aggregation of the Alzheimer\u2019s peptide","volume":"1","author":"Kim","year":"2006","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib33","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0092-8674(93)90635-4","article-title":"Seeding \u201cone-dimensional crystallization\u201d of amyloid: a pathogenic mechanism in Alzheimer\u2019s disease and scrapie?","volume":"73","author":"Jarrett","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.jmb.2007.12.079_bib34","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/pro.5560020312","article-title":"Thioflavin T interaction with synthetic Alzheimer\u2019s disease \u03b2-amyloid peptides: detection of amyloid aggregation in solution","volume":"2","author":"Levine","year":"1993","journal-title":"Protein Sci."},{"key":"10.1016\/j.jmb.2007.12.079_bib35","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1073\/pnas.93.7.2996","article-title":"Enhanced pathologic properties of Dutch-type mutant amyloid \u03b2-protein","volume":"93","author":"Davis","year":"1996","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2007.12.079_bib36","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1021\/bi051952q","article-title":"Experimental constraints on quaternary structure in Alzheimer\u2019s \u03b2-amyloid fibrils","volume":"45","author":"Petkova","year":"2006","journal-title":"Biochemistry"},{"key":"10.1016\/j.jmb.2007.12.079_bib37","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1126\/science.1105850","article-title":"Self-propagating, molecular-level polymorphism in Alzheimer\u2019s \u03b2-amyloid fibrils","volume":"307","author":"Petkova","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.jmb.2007.12.079_bib38","doi-asserted-by":"crossref","first-page":"16742","DOI":"10.1073\/pnas.262663499","article-title":"A structural model for Alzheimer\u2019s \u03b2-amyloid fibrils based on experimental constraints from solid state NMR","volume":"99","author":"Petkova","year":"2002","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2007.12.079_bib39","doi-asserted-by":"crossref","first-page":"17342","DOI":"10.1073\/pnas.0506723102","article-title":"3D structure of Alzheimer\u2019s amyloid-\u03b2(1\u201342) fibrils","volume":"102","author":"L\u00fchrs","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2007.12.079_bib40","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1006\/jmbi.2000.3514","article-title":"Nature disfavors sequences of alternating polar and nonpolar amino acids: implications for amyloidogenesis","volume":"296","author":"Broome","year":"2000","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib41","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.jmb.2004.06.043","article-title":"Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains","volume":"341","author":"Dubay","year":"2004","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib42","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1371\/journal.pbio.0050290","article-title":"Systematic in vivo analysis of the intrinsic determinants of amyloid \u03b2 pathogenicity","volume":"5","author":"Luheshi","year":"2007","journal-title":"PLoS Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib43","doi-asserted-by":"crossref","first-page":"32860","DOI":"10.1074\/jbc.M104135200","article-title":"Pathogenic effects of D23N Iowa mutant amyloid \u03b2-protein","volume":"276","author":"Van Nostr","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2007.12.079_bib44","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nn0901-887","article-title":"The \u2018Arctic\u2019 APP mutation (E693G) causes Alzheimer\u2019s disease by enhanced A\u03b2 protofibril formation","volume":"4","author":"Nilsberth","year":"2001","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.jmb.2007.12.079_bib45","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.nbd.2005.03.007","article-title":"Small non-fibrillar assemblies of amyloid-\u03b2 protein bearing the Arctic mutation induce rapid neuritic degeneration","volume":"20","author":"Whalen","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.jmb.2007.12.079_bib46","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1006\/jmbi.1996.0049","article-title":"An approach to random mutagenesis of DNA using mixtures of triphosphate derivatives of nucleoside analogues","volume":"255","author":"Zaccolo","year":"1996","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2007.12.079_bib47","first-page":"240","article-title":"Trifluoroacetic acid pretreatment reproducibly disaggregates the amyloid-\u03b2 peptide","volume":"4","author":"Jao","year":"1997","journal-title":"Amyloid J. Int. Exp. Clin. Invest."}],"container-title":["Journal of Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022283608000193?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022283608000193?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T21:31:36Z","timestamp":1557178296000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022283608000193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["S0022283608000193"],"URL":"https:\/\/doi.org\/10.1016\/j.jmb.2007.12.079","relation":{},"ISSN":["0022-2836"],"issn-type":[{"value":"0022-2836","type":"print"}],"subject":[],"published":{"date-parts":[[2008,3]]}}}