{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:06:25Z","timestamp":1779512785580,"version":"3.53.1"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer\u2019s disease (AD), especially during anti-amyloid-\u03b2 (A\u03b2) monoclonal antibody (A\u03b2-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic A\u03b2-mAb therapy and their modulation by the peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) agonist pioglitazone. AppNL-G-F knock-in mice underwent TSPO-PET and A\u03b2-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, A\u03b2-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to A\u03b2-mAb that appeared lower with pioglitazone co-treatment. Both mono- and combination therapy were associated with altered temporal and spatial dynamics of the TSPO-PET signal. In addition, we applied a previously validated microglia desynchronization index based on TSPO-PET connectivity, which captured individual variation in regional TSPO-PET organization and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. TSPO-PET therefore enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-A\u03b2 immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD.<\/jats:p>","DOI":"10.3390\/ijms27104632","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:53:24Z","timestamp":1779371604000},"page":"4632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tracking of Neuroinflammation Dynamics During Combined Anti-\u03b2-Amyloid Therapy (AAT) and Immunomodulation in a Preclinical Alzheimer\u2019s Disease Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Karin","family":"Wind-Mark","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4669-2113","authenticated-orcid":false,"given":"Lea H.","family":"Kunze","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Willem","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-2761","authenticated-orcid":false,"given":"Giovanna","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Giudici","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Nuscher","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0986-2929","authenticated-orcid":false,"given":"Guido","family":"Boening","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-1817","authenticated-orcid":false,"given":"Franz J.","family":"Gildehaus","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lindner","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3372-6046","authenticated-orcid":false,"given":"Rudolf A.","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[{"name":"Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany"},{"name":"Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE 413 90 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-7765","authenticated-orcid":false,"given":"Johannes S.","family":"Gn\u00f6rich","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9247-2843","authenticated-orcid":false,"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, 81377 Munich, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Munich, 80336 Munich, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91052 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-088X","authenticated-orcid":false,"given":"Artem","family":"Zatcepin","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/alz.12694","article-title":"Global estimates on the number of persons across the Alzheimer\u2019s disease continuum","volume":"19","author":"Gustavsson","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40259-023-00633-2","article-title":"Anti-amyloid monoclonal antibodies for the treatment of Alzheimer\u2019s disease","volume":"38","author":"Cummings","year":"2024","journal-title":"BioDrugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jalz.2011.05.2351","article-title":"Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer\u2019s Association Research Roundtable Workgroup","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3348\/kjr.2024.0105","article-title":"Amyloid-related imaging abnormalities in the era of anti-amyloid beta monoclonal antibodies for Alzheimer\u2019s disease: Recent updates on clinical and imaging features and MRI monitoring","volume":"25","author":"Jeong","year":"2024","journal-title":"Korean J. 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