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Twenty-two participants of a clinical trial of active amyloid-\u03b242 immunization (AN1792, Elan Pharmaceuticals) or placebo were studied. Comprehensive post-mortem neuropathological assessments were performed from 4 months to 15 years after the trial. We analysed the relationships between the topographical distribution of amyloid-\u03b2 removal from the cerebral cortex and tau pathology, cerebrovascular territories, plasma anti-AN1792 antibody titres and late cognitive status. Seventeen of 22 (77%) participants had Alzheimer\u2019s neuropathological change, whereas 5 of 22 (23%) had alternative causes for dementia (progressive supranuclear palsy = 1, Lewy body disease = 1, vascular brain injury = 1, and frontotemporal lobar degeneration = 2). Nineteen of the 22 participants had received the active agent, three the placebo. Fourteen of 16 (88%) patients with Alzheimer\u2019s disease receiving the active agent had evidence of plaque removal (very extensive removal = 5, intermediate = 4, very limited = 5, no removal = 2). Of particular note, two Alzheimer\u2019s patients who died 14 years after immunization had only very sparse or no detectable plaques in all regions examined. There was a significant inverse correlation between post-vaccination peripheral blood anti-AN1792 antibody titres and post-mortem plaque scores (\u03c1 = \u2212 0.664, P = 0.005). Cortical foci cleared of plaques contained less tau than did cortex with remaining plaques, but the overall distribution of tangles was extensive (Braak V\/VI). In conclusion, patients with Alzheimer\u2019s disease actively immunized against amyloid-\u03b2 can remain virtually plaque-free for 14 years. The extent of plaque removal is related to the immune response. This long duration of efficacy is important in support of active immunization protocols as therapy for, or potentially prevention of, neurodegeneration-associated protein accumulations. Inclusion of patients without Alzheimer\u2019s disease in Alzheimer\u2019s therapy trials is a problem for assessing the efficacy of treatment. Despite modification of Alzheimer\u2019s pathology, most patients had progressed to severe dementia, notably including the five with very extensive plaque removal, possibly due to continued tau propagation. Neuropathology follow-up of patients in therapeutic trials provides valuable information on the causes of dementia and effects of treatment.<\/jats:p>","DOI":"10.1093\/brain\/awz142","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T07:15:30Z","timestamp":1557386130000},"page":"2113-2126","source":"Crossref","is-referenced-by-count":196,"title":["Persistent neuropathological effects 14 years following amyloid-\u03b2 immunization in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"142","author":[{"given":"James A R","family":"Nicoll","sequence":"first","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK"},{"name":"Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R","family":"Buckland","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte H","family":"Harrison","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Page","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, Faculty of Medicine, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Harris","sequence":"additional","affiliation":[{"name":"Public Health Sciences and Medical Statistics, Faculty of Medicine, University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Love","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W","family":"Neal","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, University Hospital of Wales, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Holmes","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK"},{"name":"Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-130X","authenticated-orcid":false,"given":"Delphine","family":"Boche","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, 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