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However, studies assessing the full spectrum of neurodegenerative pathologies using modern consensus and staging criteria remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to elucidate the progression of neurodegenerative pathologies in DS and to explore the prevalence of comorbid pathologies across a broad age range (0\u201376 years), using comprehensive neuropathological assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a two-phase analysis. First, we investigated an institutional dataset, followed by a pooled analysis incorporating data from the National Alzheimer's Coordinating Center and four published studies. Pathologies assessed included amyloid-\u03b2 (A\u03b2), tau, \u03b1-synuclein, TDP-43, cerebral amyloid angiopathy (CAA), other cerebrovascular diseases (CVD), hippocampal sclerosis (HS), and basal ganglia mineralizations (BGM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Diffuse A\u03b2 plaques appeared by age 11, with neuritic plaques emerging in the mid-thirties. Mild tau pathology, including pre-tangles and neuropil threads, first emerged in the second decade, with neurofibrillary tangles fully present in the fourth decade, always concurrent with A\u03b2 plaques. All individuals over 30 exhibited ADNC. \u03b1-Synuclein pathology was observed in 27% of cases, while aging-related tau astrogliopathy (ARTAG), HS, and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were rare. CVD was present in approximately 60%, CAA was nearly universal (98%) after age 50, and 18% had BGM. Brain weight was consistently below the 25th percentile, even in younger individuals without ADNC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DS shows a distinct neurodegenerative trajectory with early A\u03b2 deposition. CAA, arteriolosclerosis, BGM, and \u03b1-synuclein pathology were highly prevalent, while ARTAG and LATE-NC were infrequently observed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251362762","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T06:30:36Z","timestamp":1754893836000},"page":"835-856","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of neurodegenerative pathologies in adult and pediatric subjects with Down syndrome"],"prefix":"10.1177","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-4401","authenticated-orcid":false,"given":"Fatih","family":"Canan","sequence":"first","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Wick","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack M","family":"Raisanen","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo J","family":"Hatanpaa","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-5517","authenticated-orcid":false,"given":"Timothy E","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Charles L","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8840-5106","authenticated-orcid":false,"given":"Elena V","family":"Daoud","sequence":"additional","affiliation":[{"name":"Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.127"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1706537"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.105.2.102"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2788.2006.00902.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12390"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlae110"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.56"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012388"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3983"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00437-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0132-6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0910-3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1985.04060100083029"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"e_1_3_3_17_2","article-title":"The national institute on aging, and Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer's disease","volume":"18","author":"Consensus recommendations for the postmortem diagnosis of Alzheimer's disease","year":"1997","unstructured":"Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. 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