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Still, a large-scale comparison of the in vivo PET uptake to quantitative <jats:italic>post-mortem<\/jats:italic> tau pathology and to other co-pathologies is lacking. Here, we examined the correlation between in vivo [<jats:sup>18<\/jats:sup>F]flortaucipir PET uptake and quantitative <jats:italic>post-mortem<\/jats:italic> tau pathology in corresponding brain regions from the AVID A16 end-of-life study (<jats:italic>n<\/jats:italic>\u2009=\u200963). All participants underwent [<jats:sup>18<\/jats:sup>F]flortaucipir PET scans prior to death, followed by a detailed <jats:italic>post-mortem<\/jats:italic> neuropathological examination using AT8 (tau) immunohistochemistry. Correlations between [<jats:sup>18<\/jats:sup>F]flortaucipir standardized uptake value ratios (SUVRs) and AT8 immunohistochemistry were assessed across 18 regions-of-interest (ROIs). To assess [<jats:sup>18<\/jats:sup>F]flortaucipir specificity and level of detection for tau pathology, correlations between [<jats:sup>18<\/jats:sup>F]flortaucipir SUVR and neuritic plaque score and TDP-43 stage were also computed and retention was further assessed in individuals with possible primary age-related tauopathy (PART), defined as Thal phase\u2009\u2264\u20092 and Braak stage I\u2013IV. We found modest-to-strong correlations between in vivo [<jats:sup>18<\/jats:sup>F]flortaucipir SUVR and <jats:italic>post-mortem<\/jats:italic> tau pathology density in corresponding brain regions in all neocortical regions analyzed (rho-range\u2009=\u20090.61\u20130.79, p\u2009&lt;\u20090.0001 for all). The detection threshold of [<jats:sup>18<\/jats:sup>F]flortaucipir PET was determined to be 0.85% of surface area affected by tau pathology in a temporal meta-ROI, and 0.15% in a larger cortical meta-ROI. No significant associations were found between [<jats:sup>18<\/jats:sup>F]flortaucipir SUVRs and <jats:italic>post-mortem<\/jats:italic> tau pathology in individuals with possible PART. Further, there was no correlation observed between [<jats:sup>18<\/jats:sup>F]flortaucipir and level of amyloid-\u03b2 neuritic plaque load (rho-range\u2009=\u2009\u2009\u2013\u20090.16\u20130.12; <jats:italic>p<\/jats:italic>\u2009=\u20090.48\u20130.61) or TDP-43 stage (rho-range\u2009=\u2009\u2009\u2013\u20090.10 to \u2009\u2013\u20090.30; <jats:italic>p<\/jats:italic>\u2009=\u20090.18\u20130.65). In conclusion, our in vivo vs <jats:italic>post-mortem<\/jats:italic> study shows that the in vivo [<jats:sup>18<\/jats:sup>F]flortaucipir PET signal primarily reflects tau pathology, also at relatively low densities of tau proteinopathy, and does not bind substantially to tau neurites in neuritic plaques or in individuals with PART.<\/jats:p>","DOI":"10.1007\/s00401-024-02801-2","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T08:02:27Z","timestamp":1726732947000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Association of in vivo retention of [18f] flortaucipir pet with tau neuropathology in corresponding brain regions"],"prefix":"10.1007","volume":"148","author":[{"given":"Tove","family":"Freiburghaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Pawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Oliveira Hauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Ossenkoppele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Strandberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Leuzy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Rittmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cilia","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Pontecorvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7147-0112","authenticated-orcid":false,"given":"Ruben","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"2801_CR1","doi-asserted-by":"publisher","DOI":"10.54294\/uvnhin","author":"B Avants","year":"2009","unstructured":"Avants B, Tustison NJ, Song G (2009) Advanced normalization tools V1.0. 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AL serves as a consultant to Enigma Biomedical USA. CT has been supported by fellowships from the Canadian Institutes of Health Research (CIHR) and Quebec\u2019s Health Research Funds (FRQS). RO has received research funding\/support from Avid Radiopharmaceuticals, Janssen Research & Development, Roche, Quanterix and Optina Diagnostics, has given lectures in symposia sponsored by GE Healthcare, is an advisory board member for Asceneuron and a steering committee member for Bristol Myers Squibb. All the aforementioned has been paid to the institutions. MJP is a full-time employee of Eli Lilly and Company and own stock in the company. TGB is a consultant for Aprinoia Therapeutics, Vivid Genomics, and Avid Radiopharmaceutical, and is a scientific advisory board member for Vivid Genomics. RS has received a speaker fee from Roche. OH has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, C2N Diagnostics, Eli Lilly, Eisai, Fujirebio, GE Healthcare, and Roche. In the past 2 years, he has received consultancy\/speaker fees from Alzpath, BioArctic, Biogen, Bristol Meyer Squibb, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi, and Siemens.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"44"}}