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We investigate the neuroanatomical distribution of activated myeloid cells, astrocytes, and complement alongside amyloid\u2010\u03b2 and phosphorylated tau in a clinically well\u2010defined prospectively collected AD cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinical variants were diagnosed antemortem, and brain tissue was collected post\u2010mortem. Typical AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200910), behavioural\/dysexecutive AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u20096), posterior cortical atrophy (PCA) AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u20093), and controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200910) were neuropathologically assessed for AD neuropathology, concurrent pathology including Lewy body disease, limbic\u2010predominant age\u2010related TDP\u201043 encephalopathy neuropathologic change (LATE\u2010NC), and vascular pathology. For quantitative assessment, we analysed the corticolimbic distribution of phosphorylated tau, amyloid\u2010\u03b2, CD68, MHC\u2010II, C4b, and glial fibrillary acidic protein (GFAP) using digital pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Phosphorylated tau was distinctly distributed in each variant. In all variants, amyloid\u2010\u03b2 was neocortical\u2010dominant, with a notable increase in the middle frontal cortex of behavioural\/dysexecutive AD. Typical AD and PCA AD had no concurrent Lewy body disease, whereas three out of six cases with behavioural\/dysexecutive AD did. LATE\u2010NC stage &gt;0 was observed in three AD cases, two typical AD (stage 1\/3), and one behavioural\/dysexecutive AD (stage 2\/3). Vascular pathology was present in each variant. In typical AD, CD68 and MHC\u2010II were hippocampal\u2010dominant. In behavioural\/dysexecutive AD, C4b was elevated in the middle frontal and inferior parietal cortex. In PCA AD, MHC\u2010II was increased in the fusiform gyrus, and GFAP in parietal cortices. Correlations between AD neuropathology and neuroinflammation were distinct within variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggests that different involvement of neuroinflammation may add to clinical heterogeneity in AD, which has implications for neuroinflammation\u2010based biomarkers and future therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.13009","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T05:04:50Z","timestamp":1728882290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alzheimer's disease clinical variants show distinct neuroinflammatory profiles with neuropathology"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4922-3286","authenticated-orcid":false,"given":"Baayla D. C.","family":"Boon","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Florida  Jacksonville FL USA"},{"name":"Department of Pathology Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Neurology Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Anatomy and Neurosciences Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Normal Aging Brain Collection Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience, program Neurodegeneration  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Frigerio","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurosciences Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Normal Aging Brain Collection Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience, program Neurodegeneration  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danae","family":"de Gooijer","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjado H. J.","family":"Morrema","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bol","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurosciences Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Normal Aging Brain Collection Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience, program Neurodegeneration  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvon","family":"Galis \u2010 de Graaf","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurosciences Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Normal Aging Brain Collection Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience, program Neurodegeneration  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Netherlands Brain Bank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Florida  Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Normal Aging Brain Collection Amsterdam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven J.","family":"van der Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Clinical Genetics Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henne","family":"Holstege","sequence":"additional","affiliation":[{"name":"Department of Neurology Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Clinical Genetics Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma D. 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