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In animal models of amyloidosis, local immune activation is centered around A\u03b2 plaques, which are usually of uniform morphology, dependent on the transgenic model used. In postmortem human brains a diversity of A\u03b2 plaque morphologies is seen including diffuse plaques (non\u2010neuritic plaques, non\u2010NP), dense\u2010core plaques, cotton\u2010wool plaques, and NP. In a recent study, we demonstrated that during the progression of Alzheimer's disease neuropathologic changes (ADNC), a transformation of non\u2010NP into NP occurs which is tightly linked to the emergence of cortical, but not hippocampal neurofibrillary tangle (NFT) pathology. This highlights the central role of NP in AD pathogenesis as well as brain region\u2010specific differences in NP formation. In order to correlate the transformation of plaque types with local immune activation, we quantified the clustering and phenotype of microglia and accumulation of astrocytes around non\u2010NP and NP during the progression of ADNC. We hypothesize that glial clustering occurs in response to formation of neuritic dystrophy around NP. First, we show that Iba1\u2010positive microglia preferentially cluster around NP. Utilizing microglia phenotypic markers, we furthermore demonstrate that CD68\u2010positive phagocytic microglia show a strong preference to cluster around NP in both the hippocampus and frontal cortex. A similar preferential clustering is observed for CD11c and ferritin\u2010positive microglia in the frontal cortex, while this preference is less pronounced in the hippocampus, highlighting differences between hippocampal and cortical A\u03b2 plaques. Glial fibrillary acidic protein\u2010positive astrocytes showed a clear preference for clustering around NP in both the frontal cortex and hippocampus. These data support the notion that NP are intimately associated with the neuroimmune response in AD and underscore the importance of the interplay of protein deposits and the immune system in the pathophysiology of AD.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16275-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16275","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T07:36:03Z","timestamp":1733816163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Preferential clustering of microglia and astrocytes around neuritic plaques during progression of Alzheimer's disease neuropathological changes"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-1128","authenticated-orcid":false,"given":"Wangchen","family":"Tsering","sequence":"first","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Department of Neuroscience, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"McKnight Brain Institute, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"de la Rosa","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle Y.","family":"Ruan","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Philips","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Department of Pathology, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9824-2064","authenticated-orcid":false,"given":"Tim","family":"Bathe","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Department of Pathology, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9450-4520","authenticated-orcid":false,"given":"Jonathan A.","family":"Villareal","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Department of Pathology, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-2149","authenticated-orcid":false,"given":"Stefan","family":"Prokop","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"McKnight Brain Institute, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Department of Pathology, College of Medicine University of Florida  Gainesville Florida USA"},{"name":"Norman Fixel Institute for Neurological Diseases University of Florida  Gainesville Florida 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