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Multiple preprocessing pipelines for tau-PET quantification have been described, with satisfactory performance but direct comparisons remain scarse. Our study evaluates the comparability of two commonly used PET preprocessing methods, respectively in native and standard spaces, in quantifying tau deposition and in their ability to discriminate AD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>209 subjects were included from the Geneva memory clinic including cognitively unimpaired (CU) individuals, mild cognitive impairment (MCI) and dementia patients. Images were processed in native and standard space using inferior cerebellar grey matter as reference region. Standardized uptake value ratios (SUVR) were extracted from AD-specific regions. Correlations between SUVR obtained by different methods and plasma biomarkers were assessed. ROC analyses compared the ability of the two methods to discriminate visually assessed tau status, amyloid-positive cognitively impaired from amyloid-negative CU, and subjects with declining cognition over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SUVR from the two methods were strongly correlated across all regions. However, SUVR values obtained with standard space method showed higher values. SUVR in the medial temporal lobe from native space processing provided a greater accuracy in discriminating positive scans and identifying subjects with cognitive decline. For all other analyses methods performed equally well. The correlation with plasma biomarkers was comparably high with both methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      While preprocessing in native and standard space is adequate for quantifying\n                      <jats:sup>18<\/jats:sup>\n                      F-Flortaucipir PET and for discriminating AD patients, higher accuracy can be obtained in the mesial temporal regions and to predict cognitive decline using processing in native space.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07452-3","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T02:08:47Z","timestamp":1752890927000},"page":"480-490","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of two preprocessing methods for 18F-Flortaucipir PET quantification in Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"53","author":[{"given":"Elif","family":"Harput","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora Elisa","family":"Peretti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Scheffler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni B.","family":"Frisoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Garibotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3518-436X","authenticated-orcid":false,"given":"Cecilia","family":"Boccalini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"7452_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","volume":"9","author":"CR Jack","year":"2010","unstructured":"Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. 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Each subject or their relatives provided voluntary written informed consent to participate in the studies.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"VG received research support and speaker fees through her institution from Healthcare, Siemens Healthineers, Novo Nordisk. Janssen and Novartis. GBF has received support, payment, consulting fees, or honoraria through his institution for lectures, presentations, speaker bureaus, manuscript writing, or educations events from: Biogen, Roche, Diadem, Novo Nordisk, GE Healthcare, OM Pharma, and Eisai. GA has served at scientific advisory boards and consultants for Roche and Lilly and received honoraria for lectures from Lilly and Schwabe Pharma. HZ has served at scientific advisory boards and\/ or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant and at advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Julius Clinical, Lilly, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials, and participated in educational programs for Biogen, Eisai, and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this article. The other authors have no conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}