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Prion-like A\u03b2 polymorphs, or \u201cstrains\u201d, can have varying pathogenicity and may underlie the phenotypic heterogeneity of the disease. In order to develop effective AD therapies, it is critical to identify the strains of A\u03b2 that might arise prior to the onset of clinical symptoms and understand how they may change with progressing disease. Down syndrome (DS), as the most common genetic cause of AD, presents promising opportunities to compare such features between early and advanced AD. In this work, we evaluate the neuropathology and A\u03b2 strain profile in the post-mortem brain tissues of 210 DS, AD, and control individuals. We assayed the levels of various A\u03b2 and tau species and used conformation-sensitive fluorescent probes to detect differences in A\u03b2 strains among individuals and populations. We found that these cohorts have some common but also some distinct strains from one another, with the most heterogeneous populations of A\u03b2 emerging in subjects with high levels of AD pathology. The emergence of distinct strains in DS at these later stages of disease suggests that the confluence of aging, pathology, and other DS-linked factors may favor conditions that generate strains that are unique from sporadic AD.<\/jats:p>","DOI":"10.1186\/s40478-021-01298-0","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T05:15:10Z","timestamp":1640582110000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Emergence of distinct and heterogeneous strains of amyloid beta with advanced Alzheimer\u2019s disease pathology in Down syndrome"],"prefix":"10.1186","volume":"9","author":[{"given":"Alison M.","family":"Maxwell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna M.","family":"Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilder","family":"Schaaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihovil","family":"Mladinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vee P.","family":"Prasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"DeGrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-5360","authenticated-orcid":false,"given":"Carlo","family":"Condello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"issue":"19","key":"1298_CR1","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","volume":"80","author":"LE Hebert","year":"2013","unstructured":"Hebert LE, Weuve J, Scherr PA, Evans DA (2013) Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census. 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