{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:31:42Z","timestamp":1790713902967,"version":"4.1.0"},"reference-count":112,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Doctoral Merit Scholarship Program for Foreign Students"},{"name":"Fonds de Recherche du Quebec\u2013Nature et technologies"},{"name":"National Council of Science and Technology"},{"name":"J\u00e9r\u00f4me L\u00e9jeune Foundation"},{"name":"Fonds de Recherche du Quebec-Sant\u00e9"},{"name":"T-32 \u2018Training in the Neurobiology of Aging\u2019","award":["AG000096"],"award-info":[{"award-number":["AG000096"]}]},{"DOI":"10.13039\/100008582","name":"McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008582","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute on Aging \u2013 National Institutes of Health","award":["1R01AG056850-01A1"],"award-info":[{"award-number":["1R01AG056850-01A1"]}]},{"name":"Alzheimer's Disease Research Center","award":["AG16573 and AG08051"],"award-info":[{"award-number":["AG16573 and AG08051"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-97776"],"award-info":[{"award-number":["MOP-97776"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000143","name":"Alzheimer Society of Canada","doi-asserted-by":"publisher","award":["241755"],"award-info":[{"award-number":["241755"]}],"id":[{"id":"10.13039\/501100000143","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epidemiological and experimental studies suggest that a disease-aggravating neuroinflammatory process is present at preclinical stages of Alzheimer\u2019s disease. Given that individuals with Down syndrome are at increased genetic risk of Alzheimer\u2019s disease and therefore develop the spectrum of Alzheimer\u2019s neuropathology in a uniform manner, they constitute an important population to study the evolution of neuroinflammation across the Alzheimer\u2019s continuum. Therefore, in this cross-sectional study, we characterized the brain inflammatory profile across the lifespan of individuals with Down syndrome. Microglial morphology and inflammatory cytokine expression were analysed by immunohistochemistry and electrochemiluminescent-based immunoassays in the frontal cortex from foetuses to adults with Down syndrome and control subjects (16 gestational weeks to 64 years), totalling 127 cases. Cytokine expression in mixed foetal primary cultures and hippocampus of adults with Down syndrome, as well as the effects of sex on cytokine expression were also analysed. A higher microglial soma size-to-process length ratio was observed in the frontal cortex of children and young adults with Down syndrome before the development of full-blown Alzheimer\u2019s pathology. Moreover, young adults with Down syndrome also displayed increased numbers of rod-like microglia. Increased levels of interleukin-8 and interleukin-10 were observed in children with Down syndrome (1\u201310 years; Down syndrome n\u2009=\u20095, controls n\u2009=\u200910) and higher levels of interleukin-1\u03b2, interleukin-1\u03b1, interleukin-6, interleukin-8, interleukin-10, interleukin-15, eotaxin-3, interferon gamma-induced protein 10, macrophage-derived chemokine, and macrophage inflammatory protein-beta, were found in young adults with Down syndrome compared to euploid cases (13\u201325 years, Down syndrome n\u2009=\u20096, controls n\u2009=\u200924). Increased cytokine expression was also found in the conditioned media of mixed cortical primary cultures from second trimester foetuses with Down syndrome (Down syndrome n\u2009=\u20097, controls n\u2009=\u20097). Older adults with Down syndrome (39\u201368 years, Down syndrome n\u2009=\u200922, controls n\u2009=\u200916) displayed reduced levels of interleukin-10, interleukin-12p40, interferon-gamma and tumour necrosis factor-alpha. Microglia displayed larger somas and shorter processes. Moreover, an increase in dystrophic microglia and rod-like microglia aligning to neurons harbouring tau pathology were also observed. Sex stratification analyses revealed that females with Down syndrome had increased interleukin-6 and interleukin-8 levels compared to males with Down syndrome. Finally, multivariate projection methods identified specific cytokine patterns among individuals with Down syndrome. Our findings indicate the presence of an early and evolving neuroinflammatory phenotype across the lifespan in Down syndrome, a knowledge that is relevant for the discovery of stage-specific targets and for the design of possible anti-inflammatory trials against Alzheimer\u2019s disease in this population.<\/jats:p>","DOI":"10.1093\/brain\/awaa326","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T23:40:29Z","timestamp":1599694829000},"page":"3653-3671","source":"Crossref","is-referenced-by-count":139,"title":["Evolution of neuroinflammation across the lifespan of individuals with Down syndrome"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7962-7433","authenticated-orcid":false,"given":"Lisi","family":"Flores-Aguilar","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Florencia","family":"Iulita","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada"},{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"},{"name":"Alzheimer-Down Unit, Fundaci\u00f3n Catalana S\u00edndrome de Down, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Kovecses","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria D","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, UCI-MIND Institute, and Center for the Neurobiology of Learning and Memory, University of California, Irvine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0490-6128","authenticated-orcid":false,"given":"Sarah M","family":"Levi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1974-5822","authenticated-orcid":false,"given":"Yian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, New York University, Grossman School of Medicine, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manor","family":"Askenazi","sequence":"additional","affiliation":[{"name":"Biomedical Hosting LLC, Arlington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-8966","authenticated-orcid":false,"given":"Thomas","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Pathology, and Psychiatry, Center for Cognitive Neurology, New York University, Grossman School of Medicine, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Busciglio","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, UCI-MIND Institute, and Center for the Neurobiology of Learning and Memory, University of California, Irvine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7962-7433","authenticated-orcid":false,"given":"A Claudio","family":"Cuello","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal, Canada"},{"name":"Department of 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