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Tau aggregates of different sizes and shapes are formed, which ultimately lead to the deposition of fibrillar tangles. We used single\u2010molecule techniques to characterize tau aggregates in the middle temporal gyrus and somatosensory cortex in post\u2010mortem brain homogenates at different Braak stages from patients with AD. Total and phosphorylated tau aggregates increased dramatically in late Braak stages. The aggregates showed greater multi\u2010site phosphorylation with increased Braak stage, but there was only a moderate change in the aggregate size distribution. Paired single nuclei transcriptomic analyses provided evidence for greater pro\u2010inflammatory microglial and complement pathway activation with increasing phosphorylated tau aggregate concentration and length. Based on this correlation, we hypothesize a cascade of disease progression in which microglial inflammation induces tau aggregation in neighboring neurons that, in turn, further enhances inflammation and the spread of tau pathology to increase the concentration of small tau aggregates.<\/jats:p>","DOI":"10.1002\/advs.77453","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:45:22Z","timestamp":1788187522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tau Aggregate Imaging and Transcriptomics of Alzheimer's Disease Brain at Different Stages of Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-9318","authenticated-orcid":false,"given":"Elizabeth A.","family":"English","sequence":"first","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8443-4469","authenticated-orcid":false,"given":"Dorothea","family":"B\u00f6ken","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-9328","authenticated-orcid":false,"given":"Matthew W.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-2332","authenticated-orcid":false,"given":"Matthew R.","family":"Cheetham","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8459-0591","authenticated-orcid":false,"given":"Johanna S.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Imperial College London  London UK"},{"name":"UK Dementia Research Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-7715","authenticated-orcid":false,"given":"Georg","family":"Meisl","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S. 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