{"id":4583,"date":"2020-06-22T18:07:05","date_gmt":"2020-06-22T22:07:05","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/evidence-of-intraneuronal-a%ce%b2-accumulation-preceding-tau-pathology-in-the-entorhinal-cortex-2\/"},"modified":"2024-12-03T14:57:05","modified_gmt":"2024-12-03T19:57:05","slug":"evidence-of-intraneuronal-a%ce%b2-accumulation-preceding-tau-pathology-in-the-entorhinal-cortex-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/evidence-of-intraneuronal-a%ce%b2-accumulation-preceding-tau-pathology-in-the-entorhinal-cortex-2\/","title":{"rendered":"Evidence of intraneuronal A\u03b2 accumulation preceding tau pathology in the entorhinal cortex"},"content":{"rendered":"<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Abstract<\/h2>\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<p>Growing evidence gathered from transgenic animal models of Alzheimer\u2019s disease (AD) indicates that the intraneuronal accumulation of amyloid-\u03b2 (A\u03b2) peptides is an early event in the AD pathogenesis, producing cognitive deficits before the deposition of insoluble plaques. Levels of soluble A\u03b2 are also a strong indicator of synaptic deficits and concurrent AD neuropathologies in post-mortem AD brain; however, it remains poorly understood how this soluble amyloid pool builds within the brain in the decades leading up to diagnosis, when a patient is likely most amenable to early therapeutic interventions. Indeed, characterizing early intracellular A\u03b2 accumulation in humans has been hampered by the lack of A\u03b2-specific antibodies, variability in the quality of available human brain tissue and the limitations of conventional microscopy. We therefore sought to investigate the development of the intraneuronal A\u03b2 pathology using extremely high-quality post-mortem brain material obtained from a cohort of non-demented subjects with short post-mortem intervals and processed by perfusion-fixation. Using well-characterized monoclonal antibodies, we demonstrate that the age-dependent intraneuronal accumulation of soluble A\u03b2 is pervasive throughout the entorhinal cortex and hippocampus, and that this phase of the amyloid pathology becomes established within AD-vulnerable regions before the deposition of A\u03b2 plaques and the formation of tau neurofibrillary tangles. We also show for the first time in post-mortem human brain that A\u03b2 oligomers do in fact accumulate intraneuronally, before the formation of extracellular plaques. Finally, we validated the origin of the A\u03b2-immunopositive pool by resolving A\u03b2- and APP\/CTF-immunoreactive sites using super resolution structured illumination microscopy. Together, these findings indicate that the lifelong accrual of intraneuronal A\u03b2 may be a potential trigger for downstream AD-related pathogenic events in early disease stages.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4583","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>Evidence of intraneuronal A\u03b2 accumulation preceding tau pathology in the entorhinal cortex - 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\/evidence-of-intraneuronal-a%ce%b2-accumulation-preceding-tau-pathology-in-the-entorhinal-cortex-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Evidence of intraneuronal A\u03b2 accumulation preceding tau pathology in the entorhinal cortex - 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