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U.S.A."],"published-print":{"date-parts":[[2018,6,26]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The aggregation of the amyloid-\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mi>\u03b2<\/mml:mi>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    (A\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mi>\u03b2<\/mml:mi>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    ) peptide into amyloid fibrils is associated with Alzheimer\u2019s disease, and several point mutations leading to early-onset disease have been identified in A\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mi>\u03b2<\/mml:mi>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    . By studying the aggregation of five disease-related mutations in vitro, we rationalize their link to familial Alzheimer\u2019s disease. We have determined the effect of mutations on the individual steps of the overall A\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mi>\u03b2<\/mml:mi>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    42 aggregation reaction and find for four of the mutations a significant increase in the rate of self-replication of fibrils, a process that has been linked to the production of toxic oligomeric species. Furthermore, by investigating the nature of the mutation, we determine the importance of the charge and size of specific residues in the aggregation of the wild-type peptide.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1803539115","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T12:16:30Z","timestamp":1528805790000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":111,"title":["On the role of sidechain size and charge in the aggregation of A\n                    <i>\u03b2<\/i>\n                    42 with familial mutations"],"prefix":"10.1073","volume":"115","author":[{"given":"Xiaoting","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Biochemistry &amp; Structural Biology, Centre for Molecular Protein Science, Department of Chemistry, Lund University, SE221 00 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-7715","authenticated-orcid":false,"given":"Georg","family":"Meisl","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Frohm","sequence":"additional","affiliation":[{"name":"Division of Biochemistry &amp; Structural Biology, Centre for Molecular Protein Science, Department of Chemistry, Lund University, SE221 00 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Thulin","sequence":"additional","affiliation":[{"name":"Division of Biochemistry &amp; Structural Biology, Centre for Molecular Protein Science, Department of Chemistry, Lund University, SE221 00 Lund, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomas P. 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