{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:17:50Z","timestamp":1780057070452,"version":"3.54.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["115372"],"award-info":[{"award-number":["115372"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The present work was undertaken to study the genetic contribution to the start of Alzheimer's disease (AD) with amyloid and tau biomarkers in cognitively intact older identical twins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied in 96 monozygotic twin\u2010pairs relationships between amyloid\u2010beta (A\u03b2) aggregation as measured by the A\u03b21\u201342\/1\u201340 ratio in cerebrospinal fluid (CSF; n = 126) and positron emission tomography (PET, n = 194), and CSF markers for A\u03b2 production (beta\u2010secretase 1, A\u03b21\u201340, and A\u03b21\u201338) and CSF tau. Associations among markers were tested with generalized estimating equations including a random effect for twin status, adjusted for age, gender, and apolipoprotein E \u03b54 genotype. We used twin analyses to determine relative contributions of genetic and\/or environmental factors to AD pathophysiological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010seven individuals (14%) had an abnormal amyloid PET, and 14 twin\u2010pairs (15%) showed discordant amyloid PET scans. Within twin\u2010pairs, A\u03b2 production markers and total\u2010tau (t\u2010tau) levels strongly correlated (\n                      <jats:italic>r<\/jats:italic>\n                      range = 0.73\u20130.86, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and A\u03b2 aggregation markers and 181\u2010phosphorylated\u2010tau (p\u2010tau) levels correlated moderately strongly (\n                      <jats:italic>r<\/jats:italic>\n                      range = 0.50\u20130.64, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Cross\u2010twin cross\u2010trait analysis showed that A\u03b21\u201338 in one twin correlated with A\u03b21\u201342\/1\u201340 ratios, and t\u2010tau and p\u2010tau levels in their cotwins (\n                      <jats:italic>r<\/jats:italic>\n                      range = \u22120.28 to 0.58, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.007). Within\u2010pair differences in A\u03b2 production markers related to differences in tau levels (\n                      <jats:italic>r<\/jats:italic>\n                      range = 0.49\u20130.61, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Twin discordance analyses suggest that A\u03b2 production and tau levels show coordinated increases in very early AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our results suggest a substantial genetic\/shared environmental background contributes to both A\u03b2 and tau increases, suggesting that modulation of environmental risk factors may aid in delaying the onset of AD pathophysiological processes. ANN NEUROL 2021;89:987\u20131000<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26048","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T12:54:55Z","timestamp":1613307295000},"page":"987-1000","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Onset of Preclinical Alzheimer Disease in Monozygotic Twins"],"prefix":"10.1002","volume":"89","author":[{"given":"Elles","family":"Konijnenberg","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-3633","authenticated-orcid":false,"given":"Jori","family":"Tomassen","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"den Braber","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"},{"name":"Department of Biological Psychology, Amsterdam Neuroscience Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"ten Kate","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maqsood","family":"Yaqub","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra D.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel G.","family":"Nivard","sequence":"additional","affiliation":[{"name":"Department of Biological Psychology, Amsterdam Neuroscience Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Vanderstichele","sequence":"additional","affiliation":[{"name":"Biomarkable bv, working for this study on behalf of ADx NeuroSciences  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Lammertsma","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart N. 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