{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:39:52Z","timestamp":1791545992860,"version":"4.3.4"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n It is unclear whether the duration of amyloid-\u03b2 (A\u03b2) pathology is associated with neurodegeneration and whether this depends on the presence of tau.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine the association of longitudinal atrophy with A\u03b2 positron emission tomography (PET)\u2013positivity (A\u03b2+) and the estimated duration of A\u03b2+ (A\u03b2+ duration), controlling for tau-positivity.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Data for this longitudinal cohort study were drawn from the Wisconsin Registry for Alzheimer Prevention and the Wisconsin Alzheimer Disease Research Center Clinical Core Study. Participants who had 2 or more magnetic resonance imaging (MRI) visits, 1 Pittsburgh compound B (PiB) PET visit, and 1 MK-6240 PET visit with other covariates available were included. A replication analysis was conducted using data from the OASIS-3 dataset. All data were collected between June 1, 2009, and January 22, 2025. Follow-up times ranged from 1.0 to 13.0 years (median [IQR], 8.8 [5.9-10.6] years).<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Sampled iterative local approximation (SILA)-estimated PiB PET uptake at baseline MRI was used to estimate A\u03b2+ and its duration at baseline MRI. MK-6240 PET uptake in the entorhinal cortex was used to create tau-positive and tau-negative groups using a threshold of 1.27 standardized uptake value ratio.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n SILA-based modeling of PiB PET data was used to obtain estimated A\u03b2+ duration at baseline MRI age. Linear mixed-effects models tested differences in atrophy between A\u03b2+ vs A\u03b2\u2212 individuals and with A\u03b2+ duration, controlling for individuals who were tau-positive (measured via MK-6240 tau PET) at their most recent PET scan within their MRI visits.\n Z<\/jats:italic>\n -scored volumes in temporo-parietal regions of interest associated with AD dementia were assessed via a robust normative approach.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 95 A\u03b2+ (median [IQR] age, 66.4 [61.1-70.4] years; 59 female [62.11%]) and 275 A\u03b2\u2212 (median [IQR] age, 60.2 [55.7-64.6] years; 183 [66.55%] female) individuals were included. A\u03b2+ (partial \u03b7\n 2<\/jats:sup>\n , 0.015-0.043) and tau-positivity (partial \u03b7\n 2<\/jats:sup>\n , 0.018-0.100) were independently associated with neurodegeneration, with generally small effect sizes. A\u03b2+ duration was associated with atrophy in a greater number of regions of interest than A\u03b2+ status alone with somewhat larger effect sizes (partial \u03b7\n 2<\/jats:sup>\n , 0.013-0.056). Results were mostly similar in the OASIS-3 dataset.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this longitudinal cohort study, subtle neurodegeneration was observed soon after the onset of A\u03b2 pathology. These results may be consistent with A\u03b2 pathology as a pathological state.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.31093","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T15:00:17Z","timestamp":1757430017000},"page":"e2531093","source":"Crossref","is-referenced-by-count":4,"title":["Abnormal Amyloid-\u03b2 Duration, Tau, and Neurodegeneration in Cranial Images"],"prefix":"10.1001","volume":"8","author":[{"given":"Henry Gilreath","family":"Stephenson","sequence":"first","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Neuroscience Training Program, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Langhough","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Jonaitis","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlian","family":"Du","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin\u2013Madison, Madison"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Van Hulle","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel A.","family":"Chin","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozioma C.","family":"Okonkwo","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Neuroscience Training Program, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Carlsson","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin\u2013Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin\u2013Madison, Madison"},{"name":"Veterans Administration William S. 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