{"id":4551,"date":"2020-06-22T16:54:23","date_gmt":"2020-06-22T20:54:23","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/early-intraneuronal-amyloid-triggers-neuron-derived-inflammatory-signaling-in-app-transgenic-rats-and-human-brain-2\/"},"modified":"2024-12-03T14:57:00","modified_gmt":"2024-12-03T19:57:00","slug":"early-intraneuronal-amyloid-triggers-neuron-derived-inflammatory-signaling-in-app-transgenic-rats-and-human-brain-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/early-intraneuronal-amyloid-triggers-neuron-derived-inflammatory-signaling-in-app-transgenic-rats-and-human-brain-2\/","title":{"rendered":"Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain"},"content":{"rendered":"<div class=\"executive-summary\">\n<h2 class=\"\">Significance<\/h2>\n<p id=\"p-4\">This work provides evidence that soluble and oligomeric amyloid protein stokes neuronal inflammation during the earliest stages of Alzheimer\u2019s disease. Identifying neuron-derived factors that engage the brain\u2019s immune system will provide insight into how vulnerable neurons might interact with other immune cells to propagate cytotoxic signaling cascades and cellular dysfunction during disease development.<\/p>\n<\/div>\n<div id=\"abstract-2\" class=\"section abstract\">\n<h2>Abstract<\/h2>\n<p id=\"p-5\">Chronic inflammation during Alzheimer\u2019s disease (AD) is most often attributed to sustained microglial activation in response to amyloid-\u03b2 (A\u03b2) plaque deposits and cell death. However, cytokine release and microgliosis are consistently observed in AD transgenic animal models devoid of such pathologies, bringing into question the underlying processes that may be at play during the earliest AD-related immune response. We propose that this plaque-independent inflammatory reaction originates from neurons burdened with increasing levels of soluble and oligomeric A\u03b2, which are known to be the most toxic amyloid species within the brain. Laser microdissected neurons extracted from preplaque amyloid precursor protein (APP) transgenic rats were found to produce a variety of potent immune factors, both at the transcript and protein levels. Neuron-derived cytokines correlated with the extent of microglial activation and mobilization, even in the absence of extracellular plaques and cell death. Importantly, we identified an inflammatory profile unique to A\u03b2-burdened neurons, since neighboring glial cells did not express similar molecules. Moreover, we demonstrate within disease-vulnerable regions of the human brain that a neuron-specific inflammatory response may precede insoluble A\u03b2 plaque and tau tangle formation. Thus, we reveal the A\u03b2-burdened neuron as a primary proinflammatory agent, implicating the intraneuronal accumulation of A\u03b2 as a significant immunological component in the AD pathogenesis.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4551","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain - 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\/early-intraneuronal-amyloid-triggers-neuron-derived-inflammatory-signaling-in-app-transgenic-rats-and-human-brain-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain - 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