{"id":4832,"date":"2021-06-08T14:34:17","date_gmt":"2021-06-08T18:34:17","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/evolution-of-neuroinflammation-across-the-lifespan-of-individuals-with-down-syndrome\/"},"modified":"2024-12-03T14:57:47","modified_gmt":"2024-12-03T19:57:47","slug":"evolution-of-neuroinflammation-across-the-lifespan-of-individuals-with-down-syndrome","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/evolution-of-neuroinflammation-across-the-lifespan-of-individuals-with-down-syndrome\/","title":{"rendered":"Evolution of neuroinflammation across the lifespan of individuals with Down syndrome"},"content":{"rendered":"<h2 id=\"226872326\" class=\"abstract-title js-splitscreen-abstract-title\">Abstract<\/h2>\n<section class=\"abstract\">\n<p class=\"chapter-para\">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\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>5, controls\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>10) 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\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>6, controls\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>24). Increased cytokine expression was also found in the conditioned media of mixed cortical primary cultures from second trimester foetuses with Down syndrome (Down syndrome\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>7, controls\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>7). Older adults with Down syndrome (39\u201368 years, Down syndrome\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>22, controls\u00a0<em>n\u2009<\/em>=<em>\u2009<\/em>16) 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.<\/p>\n<\/section>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4832","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Evolution of neuroinflammation across the lifespan of individuals with Down syndrome - CCNA - CCNV<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/evolution-of-neuroinflammation-across-the-lifespan-of-individuals-with-down-syndrome\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Evolution of neuroinflammation across the lifespan of individuals with Down syndrome - 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