{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:40:46Z","timestamp":1790833246929,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T00:00:00Z","timestamp":1487203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>The abnormal deposition of amyloid\u2010<jats:italic>\u03b2<\/jats:italic> (A<jats:italic>\u03b2<\/jats:italic>) peptides in the brain is the main neuropathological hallmark of Alzheimer's disease (AD). Amyloid deposits are formed by a heterogeneous mixture of A<jats:italic>\u03b2<\/jats:italic> peptides, among which the most studied are A<jats:italic>\u03b2<\/jats:italic>40 and A<jats:italic>\u03b2<\/jats:italic>42. A<jats:italic>\u03b2<\/jats:italic>40 is abundantly produced in the human brain, but the level of A<jats:italic>\u03b2<\/jats:italic>42 is remarkably increased in the brain of AD patients. Aside from A<jats:italic>\u03b2<\/jats:italic>40 and A<jats:italic>\u03b2<\/jats:italic>42, recent data have raised the possibility that A<jats:italic>\u03b2<\/jats:italic>43 peptides may be instrumental in AD pathogenesis. Besides its length, whether the A<jats:italic>\u03b2<\/jats:italic> aggregated form accounts for the neurotoxicity is also particularly controversial. A<jats:italic>\u03b2<\/jats:italic> fibrils are generally considered as key pathogenic substances in AD pathogenesis. Nevertheless, recent data implicated soluble A<jats:italic>\u03b2<\/jats:italic> oligomers as the main cause of synaptic dysfunction and memory loss in AD. To further address this uncertainty, we analyzed the neurotoxicity of different A<jats:italic>\u03b2<\/jats:italic> species and A<jats:italic>\u03b2<\/jats:italic> forms at the cellular level. The results showed that A<jats:italic>\u03b2<\/jats:italic>42 could form oligomers significantly faster than A<jats:italic>\u03b2<\/jats:italic>40 and A<jats:italic>\u03b2<\/jats:italic>43 and A<jats:italic>\u03b2<\/jats:italic>42 oligomers showed the greatest level of neurotoxicity. Regardless of the length of A<jats:italic>\u03b2<\/jats:italic> peptides, A<jats:italic>\u03b2<\/jats:italic> oligomers induced significantly higher cytotoxicity compared with the other two A<jats:italic>\u03b2<\/jats:italic> forms. Surprisingly, the neurotoxicity of fibrils in PC12 cells was only marginally but not significantly stronger than monomers, contrary to previous reports. Altogether, our findings demonstrate the high pathogenicity of A<jats:italic>\u03b2<\/jats:italic>42 among the three A<jats:italic>\u03b2<\/jats:italic> species and support the idea that A<jats:italic>\u03b2<\/jats:italic>42 oligomers contribute to the pathological events leading to neurodegeneration in AD. Copyright \u00a9 2017 European Peptide Society and John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/psc.2975","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T02:48:59Z","timestamp":1487299739000},"page":"245-251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Comparison of neurotoxicity of different aggregated forms of A<i>\u03b2<\/i>40, A<i>\u03b2<\/i>42 and A<i>\u03b2<\/i>43 in cell cultures"],"prefix":"10.1002","volume":"23","author":[{"given":"Lu","family":"Fu","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Sun","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Guo","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Yu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Kong","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences Jilin University  Changchun 130012 China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,16]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"PrinceMJ WimoA GuerchetMM AliGC WuY\u2010T PrinaM.World Alzheimer Report 2015 \u2010 The Global Impact of Dementia: An analysis of prevalence incidence cost and trends. 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