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U.S.A."],"published-print":{"date-parts":[[2021,11,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Alzheimer's disease (AD) patients develop amyloid deposits, containing amyloid-\u03b2 (A\u03b2) fibrils, in their brain tissue. Although amyloid is a likely contributor to AD dementia, similar amyloid loads occur in some nondemented elderly individuals. Molecular structures of A\u03b2 fibrils are known to be variable. We, therefore, investigate whether structures of A\u03b2 fibrils derived from cerebral cortical tissue of nondemented elderly subjects differ from structures from AD patients. We find statistically significant, but subtle, differences between NMR spectra of A\u03b2 fibrils from nondemented elderly subjects and analogous spectra of fibrils from AD patients. Thus, similar structures develop but with different relative populations on average. Other factors may be primary determinants of cognitive status in individuals with high amyloid loads.<\/jats:p>","DOI":"10.1073\/pnas.2111863118","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T16:56:39Z","timestamp":1635785799000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":34,"title":["Structural differences in amyloid-\u03b2 fibrils from brains of nondemented elderly individuals and Alzheimer's disease patients"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7818-4792","authenticated-orcid":false,"given":"Ujjayini","family":"Ghosh","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-0520;"},{"name":"Department of Chemistry, Michigan State University, East Lansing, MI 48824;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Ming","family":"Yau","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, University College London, London W1W 7FF, United Kingdom;"},{"name":"Institute of Prion Diseases, University College London, London W1W 7FF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-7275","authenticated-orcid":false,"given":"Robert","family":"Tycko","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720507780362245"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000283480"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.702704"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2012.01.016"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.720656"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.11.020"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(97)00023-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0806142"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.11.1509"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23797"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.09.011"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123743"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(96)00170-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.12.1571"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2008.02.008"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp062"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.07.029"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105850"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.03.017"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.035"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20814"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12683-8"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2023089118"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2991"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600749113"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao2825"},{"key":"e_1_3_4_28_2","first-page":"1","article-title":"Polymorphic A\u03b242 fibrils adopt similar secondary structure but differ in cross-strand side chain stacking interactions within the same \u03b2-sheet","volume":"10","author":"Wang H. 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