{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:09:57Z","timestamp":1792069797747,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Alzheimer disease (AD) is characterized by amyloid \u03b2 (A\u03b2) plaques and neurofibrillary tau tangles, but increasing evidence suggests that neuroinflammation also plays a key role, driven by the activation of microglia. A\u03b2 and tau pathology appear to spread along pathways of highly connected brain regions, but it remains elusive whether microglial activation follows a similar distribution pattern. Here, we assess whether connectivity is associated with microglia activation patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included 32 A\u03b2\u2010positive early AD subjects (18 women, 14 men) and 18 A\u03b2\u2010negative age\u2010matched healthy controls (10 women, 8 men) from the prospective ActiGliA (Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease) study. All participants underwent microglial activation positron emission tomography (PET) with the third\u2010generation mitochondrial 18 kDa translocator protein (TSPO) ligand [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE\u2010180 and magnetic resonance imaging (MRI) to measure resting\u2010state functional and structural connectivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that inter\u2010regional covariance in TSPO\u2010PET and standardized uptake value ratio was preferentially distributed along functionally highly connected brain regions, with MRI structural connectivity showing a weaker association with microglial activation. AD patients showed increased TSPO\u2010PET tracer uptake bilaterally in the anterior medial temporal lobe compared to controls, and higher TSPO\u2010PET uptake was associated with cognitive impairment and dementia severity in a disease stage\u2010dependent manner.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Microglial activation distributes preferentially along highly connected brain regions, similar to tau pathology. These findings support the important role of microglia in neurodegeneration, and we speculate that pathology spreads throughout the brain along vulnerable connectivity pathways. ANN NEUROL 2022;92:768\u2013781<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26465","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T06:40:16Z","timestamp":1659336016000},"page":"768-781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Microglial Activation and Connectivity in Alzheimer Disease and Aging"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-6240","authenticated-orcid":false,"given":"Boris\u2010Stephan","family":"Rauchmann","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Hospital, Ludwig Maximilian University of Munich  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases  Munich Germany"},{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield"},{"name":"Department of Neuroradiology University Hospital, 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