{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:08:27Z","timestamp":1784380107099,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Edmond J Safra Philanthropic Foundation"},{"name":"Rossy Family Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Limited comparative data exist on the molecular spectrum of amyloid-beta (A\u03b2) and tau deposition in individuals with Down syndrome (DS) and sporadic Alzheimer\u2019s disease (sAD). We assessed A\u03b2 and tau deposition severity in the temporal lobe and cerebellum of ten DS and ten sAD cases. Immunohistochemistry was performed using antibodies against eight different A\u03b2 epitopes (6F\/3D, A\u03b238, A\u03b239, A\u03b240, A\u03b242, A\u03b243, pyroglutamate A\u03b2 at third glutamic acid (A\u03b2Np3E), phosphorylated- (p-)A\u03b2 at 8th serine (A\u03b2pSer8)), and six different pathological tau epitopes (p-Ser202\/Thr205, p-Thr231, p-Ser396, Alz50, MC1, GT38). Findings were evaluated semi-quantitatively and quantitatively using digital pathology. DS cases had significantly higher neocortical parenchymal deposition (A\u03b238, A\u03b242, and A\u03b2pSer8), and cerebellar parenchymal deposition (A\u03b240, A\u03b242, A\u03b2Np3E, and A\u03b2pSer8) than sAD cases. Furthermore, DS cases had a significantly larger mean plaque size (6F\/3D, A\u03b242, A\u03b2Np3E) in the temporal lobe, and significantly greater deposition of cerebral and cerebellar A\u03b242 than sAD cases in the quantitative analysis. Western blotting corroborated these findings. Regarding tau pathology, DS cases had significantly more severe cerebral tau deposition than sAD cases, especially in the white matter (p-Ser202\/Thr205, p-Thr231, Alz50, and MC1). Greater total tau deposition in the white matter (p-Ser202\/Thr205, p-Thr231, and Alz50) of DS cases was confirmed by quantitative analysis. Our data suggest that the A\u03b2 and tau molecular signatures in DS are distinct from those in sAD.<\/jats:p>","DOI":"10.3390\/ijms241411596","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:47:38Z","timestamp":1689727658000},"page":"11596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Distinct Molecular Signatures of Amyloid-Beta and Tau in Alzheimer\u2019s Disease Associated with Down Syndrome"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-8137","authenticated-orcid":false,"given":"Shojiro","family":"Ichimata","sequence":"first","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Department of Legal Medicine, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-6321","authenticated-orcid":false,"given":"Ivan","family":"Martinez-Valbuena","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seojin","family":"Lee","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"Karakani","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"Gabor G.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 2S8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Edmond J. Safra Program in Parkinson\u2019s Disease, Rossy Program for PSP Research and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada"},{"name":"Laboratory Medicine Program, Krembil Brain Institute, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1056\/NEJMra1706537","article-title":"Down Syndrome","volume":"382","author":"Bull","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/NEN.0b013e318202bfa1","article-title":"Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome","volume":"70","author":"Wegiel","year":"2011","journal-title":"J. Neuropathol. Exp. 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