{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:26:57Z","timestamp":1787138817446,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,17]]},"group-title":"Neurology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"crossref","award":["ARUK-PG2014-1946"],"award-info":[{"award-number":["ARUK-PG2014-1946"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"crossref","award":["ARUK-PG2017-1946"],"award-info":[{"award-number":["ARUK-PG2017-1946"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SG-666374-UK BIRTH COHORT"],"award-info":[{"award-number":["SG-666374-UK BIRTH COHORT"]}],"id":[{"id":"https:\/\/ror.org\/0375f4d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CSUB19166"],"award-info":[{"award-number":["CSUB19166"]}],"id":[{"id":"https:\/\/ror.org\/05p21nq18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PR\/ylr\/18575"],"award-info":[{"award-number":["PR\/ylr\/18575"]}],"id":[{"id":"https:\/\/ror.org\/0333xzh65","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MC_UU_10019\/1"],"award-info":[{"award-number":["MC_UU_10019\/1"]}]},{"name":"Medical Research Council","award":["MC_UU_10019\/3"],"award-info":[{"award-number":["MC_UU_10019\/3"]}]},{"DOI":"10.13039\/100013790","name":"Brain Research UK","doi-asserted-by":"crossref","award":["UCC14191"],"award-info":[{"award-number":["UCC14191"]}],"id":[{"id":"10.13039\/100013790","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Quantitative amyloid-beta (A\u03b2)-PET is increasingly used in AD prevention trials. Although the Centiloid (CL) framework provides a common scale, variability persists across processing pipelines, including differences in template\/native space, partial volume correction (PVC), and reference region. These choices may influence cut-points, and in turn positivity rates, as well as longitudinal accumulation rates. We examined cut-point estimates and inter-pipeline discordance in a community cohort where many are expected to have early A\u03b2 deposition.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We analysed [\u00b9\u2078F]florbetapir PET\/MR data from predominantly cognitively unimpaired (\u223c95%) individuals aged \u223c71 years at baseline (n=433) and at follow-up (n=328; \u223c2.4-year interval) in Insight 46 (1946 British birth cohort). Centiloids were derived using the standard pipeline and ten in-house pipelines employing alternative reference regions and PVC in native space. Gaussian mixture modelling estimated cut-points with bootstrapped uncertainty. We assessed A\u03b2-discordance across pipelines as a function of standard CLs and examined follow-up CSF A\u03b242\/A\u03b240 (n=120) and PET in individuals with discordant baseline classifications.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Baseline cut-points were 10\u201323 CL across pipelines, classifying 16\u201325% as A\u03b2-positive. Reliable accumulation cut-points were 3.5\u20136 CL\/year, identifying 16\u2013 22% as accumulators. Uncertainty varied across pipelines. At baseline, 18% were discordant across PET measures, predominantly between 11\u201335 standard CLs. The discordant group showed higher A\u03b2-PET accumulation and lower CSF A\u03b242\/A\u03b240 than concordant negatives.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Disagreement between A\u03b2-PET methods was highest between 11\u201335 standard Centiloids and was frequently associated with accumulating A\u03b2. These findings highlight the importance of considering cut-point uncertainty and methodological influences when interpreting early-stage amyloidosis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Processing methods significantly influence amyloid PET Centiloid estimates<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Amyloid positivity thresholds and varied across commonly used PET methods<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>PET discordance was greatest within an intermediate range between 11\u201335 Centiloids<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Future CSF and longitudinal PET suggest PET discordance frequently reflects early amyloidosis<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.14.26360465","type":"posted-content","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:25:11Z","timestamp":1787001911000},"source":"Crossref","is-referenced-by-count":0,"title":["Amyloid-PET pipeline choice influences classification of preclinical Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3976-9461","authenticated-orcid":false,"given":"William","family":"Coath","sequence":"first","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Bollack","sequence":"additional","affiliation":[{"name":"GE HealthCare, Amersham, UK"},{"name":"Department of Medical Physics & Biomedical Engineering, UCL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J","family":"Scott","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, University College London, London, UK"},{"name":"Institute of Nuclear Medicine, University College London NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-5721","authenticated-orcid":false,"given":"Ashvini","family":"Keshavan","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom"},{"name":"UK Dementia Research Institute at UCL, University College London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7512-7856","authenticated-orcid":false,"given":"Ian B","family":"Malone","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Murray-Smith","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel J","family":"Markiewicz","sequence":"additional","affiliation":[{"name":"Hawkes Institute, Department of Computer Science, University College London, London, UK"},{"name":"Computer Science and Informatics, School of Engineering, London South Bank University, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjell","family":"Erlandsson","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A","family":"Thomas","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, University College London, London, UK"},{"name":"Advanced Research Computing Centre, UCL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Department of Medical Physics & Biomedical Engineering, UCL"},{"name":"Department of Radiology & Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Brain Imaging, Amsterdam Neuroscience, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Dickson","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, University College London, London, UK"},{"name":"Institute of Nuclear Medicine, University College London NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-1781","authenticated-orcid":false,"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Wallenberg Centre for Molecular and Translational Medicine, The University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Insight 46 team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan 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