{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:58:48Z","timestamp":1790773128181,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"crossref","award":["FRSM 3.4516.11"],"award-info":[{"award-number":["FRSM 3.4516.11"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002910","name":"F\u00e9d\u00e9ration Wallonie-Bruxelles","doi-asserted-by":"crossref","award":["ARC SLEEPDEM 17\/27-09"],"award-info":[{"award-number":["ARC SLEEPDEM 17\/27-09"]}],"id":[{"id":"10.13039\/501100002910","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["Radiomed Project"],"award-info":[{"award-number":["Radiomed Project"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"name":"General Electric Healthcare Ltd","award":["ISS290"],"award-info":[{"award-number":["ISS290"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,25]]},"abstract":"\n BACKGROUND<\/jats:title>\n Neuronal hyperexcitability characterizes the early stages of Alzheimer\u2019s disease (AD). In animals, early misfolded tau and amyloid-\u03b2 (A\u03b2) protein accumulation \u2014 both central to AD neuropathology \u2014 promote cortical excitability and neuronal network dysfunction. In healthy humans, misfolded tau and A\u03b2 aggregates are first detected, respectively, in the brainstem and frontomedial and temporobasal cortices, decades prior to the onset of AD cognitive symptoms. Whether cortical excitability is related to early brainstem tau \u2014 and its associated neuroinflammation \u2014 and cortical A\u03b2 aggregations remains unknown.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We probed frontal cortex excitability, using transcranial magnetic stimulation combined with electroencephalography, in a sample of 64 healthy late-middle\u2013aged individuals (50\u201369 years; 45 women and 19 men). We assessed whole-brain\n [18F]<\/jats:sup>\n THK5351 PET uptake as a proxy measure of tau\/neuroinflammation, and we assessed whole-brain A\u03b2 burden with\n [18F]<\/jats:sup>\n Flutemetamol or\n [18F]<\/jats:sup>\n Florbetapir radiotracers.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n We found that higher\n [18F]<\/jats:sup>\n THK5351 uptake in a brainstem monoaminergic compartment was associated with increased cortical excitability (\n r<\/jats:italic>\n = 0.29,\n P<\/jats:italic>\n = 0.02). By contrast,\n [18F]<\/jats:sup>\n THK5351 PET signal in the hippocampal formation, although strongly correlated with brainstem signal in whole-brain voxel-based quantification analyses (\n P<\/jats:italic>\n value corrected for family-wise error [\n \n P\n FWE-corrected<\/jats:sub>\n <\/jats:italic>\n ] < 0.001), was not significantly associated with cortical excitability (\n r<\/jats:italic>\n = 0.14,\n P<\/jats:italic>\n = 0.25). Importantly, no significant association was found between early A\u03b2 cortical deposits and cortical excitability (\n r<\/jats:italic>\n = \u20130.20,\n P<\/jats:italic>\n = 0.11).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n These findings reveal potential brain substrates for increased cortical excitability in preclinical AD and may constitute functional in vivo correlates of early brainstem tau accumulation and neuroinflammation in humans.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION<\/jats:title>\n EudraCT 2016-001436-35.<\/jats:p>\n <\/jats:sec>\n \n FUNDING<\/jats:title>\n F.R.S.-FNRS Belgium, Wallonie-Bruxelles International, ULi\u00e8ge, Fondation Simone et Pierre Clerdent, European Regional Development Fund.<\/jats:p>\n <\/jats:sec>","DOI":"10.1172\/jci.insight.142514","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T12:38:26Z","timestamp":1607431106000},"source":"Crossref","is-referenced-by-count":13,"title":["Early brainstem [18F]THK5351 uptake is linked to cortical hyperexcitability in healthy aging"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3142-2623","authenticated-orcid":true,"given":"Maxime","family":"Van Egroo","sequence":"first","affiliation":[{"name":"GIGA-Cyclotron Research Centre-In Vivo Imaging and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Chylinski","sequence":"additional","affiliation":[{"name":"GIGA-Cyclotron Research Centre-In Vivo Imaging and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justinas","family":"Narbutas","sequence":"additional","affiliation":[{"name":"GIGA-Cyclotron Research Centre-In Vivo Imaging and"},{"name":"Psychology and Cognitive Neuroscience Research Unit, University of Li\u00e8ge (ULi\u00e8ge), Li\u00e8ge, 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