{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:10:11Z","timestamp":1792069811997,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["BRC\u20101215\u201020014"],"award-info":[{"award-number":["BRC\u20101215\u201020014"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005224","name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["1007"],"award-info":[{"award-number":["1007"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390857198"],"award-info":[{"award-number":["390857198"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022572","name":"NIHR Sheffield Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203321"],"award-info":[{"award-number":["NIHR203321"]}],"id":[{"id":"10.13039\/501100022572","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000735","name":"University of Cambridge","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007453","name":"Stiftung VERUM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4\u2010repeat (4R) tauopathies and its role in accelerating disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We tested whether microglial activation (1) progresses in similar spatial patterns as the primary pathology tau spreads across interconnected brain regions, and (2) whether the degree of microglial activation parallels tau pathology spreading.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined in vivo associations between tau aggregation and microglial activation in 31 patients with clinically diagnosed 4R tauopathies, using 18F\u2010PI\u20102620 PET and 18F\u2010GE180 (translocator protein [TSPO]) PET. We determined tau epicenters, defined as subcortical brain regions with highest tau PET signal, and assessed the connectivity of tau epicenters to cortical regions of interest using a 3\u2010T resting\u2010state functional magnetic resonance imaging template derived from age\u2010matched healthy elderly controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 4R tauopathy patients, we found that higher regional tau PET covaries with elevated TSPO\u2010PET across brain regions that are functionally connected to each other (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.414,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Microglial activation follows similar distribution patterns as tau and distributes primarily across brain regions strongly connected to patient\u2010specific tau epicenters (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.594,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). In these regions, microglial activation spatially parallels tau distribution detectable with 18F\u2010PI\u20102620 PET.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that the spatial expansion of microglial activation parallels tau distribution across brain regions that are functionally connected to each other, suggesting that tau and inflammation are closely interrelated in patients with 4R tauopathies. The combination of in vivo tau and inflammatory biomarkers could therefore support the development of immunomodulatory strategies for disease\u2010modifying treatments in these conditions. \u00a9 2024 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.29924","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T03:45:20Z","timestamp":1721274320000},"page":"1480-1492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Neuroinflammation Parallels\n                    <scp>18F<\/scp>\n                    \u2010\n                    <scp>PI<\/scp>\n                    \u20102620 Positron Emission Tomography Patterns in Primary 4\u2010Repeat Tauopathies"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian N.","family":"Roemer","sequence":"additional","affiliation":[{"name":"Department of Neurology LMU Hospital, LMU Hospital, LMU Munich  Munich Germany"},{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine LMU Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattes","family":"Gross","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich Germany"},{"name":"Department of Nuclear Medicine LMU Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gn\u00f6rich","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine LMU Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Stephens","sequence":"additional","affiliation":[{"name":"Life Molecular Imaging  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dewenter","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Steward","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davina","family":"Biel","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7116-9741","authenticated-orcid":false,"given":"Amir","family":"Dehsarvi","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU Munich  Munich 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-5984","authenticated-orcid":false,"given":"Sabrina","family":"Katzdobler","sequence":"additional","affiliation":[{"name":"Department of Neurology LMU Hospital, LMU Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Rupprecht","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Perneczky","sequence":"additional","affiliation":[{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich  Munich Germany"},{"name":"Department of Psychiatry and Psychotherapy LMU Hospital, LMU Munich  Munich Germany"},{"name":"Aging Epidemiology Research Unit School of Public Health, Imperial College London  London UK"},{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris\u2010Stephan","family":"Rauchmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy LMU Hospital, LMU Munich  Munich Germany"},{"name":"Department of Neuroradiology LMU Hospital, LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Neurology LMU Hospital, LMU Hospital, LMU Munich  Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"Department of 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