{"id":4710,"date":"2021-02-23T14:22:25","date_gmt":"2021-02-23T19:22:25","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/plasma-p-tau231-a-new-biomarker-for-incipient-alzheimers-disease-pathology-2\/"},"modified":"2024-12-03T14:57:26","modified_gmt":"2024-12-03T19:57:26","slug":"plasma-p-tau231-a-new-biomarker-for-incipient-alzheimers-disease-pathology-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/plasma-p-tau231-a-new-biomarker-for-incipient-alzheimers-disease-pathology-2\/","title":{"rendered":"Plasma p-tau231: a new biomarker for incipient Alzheimer\u2019s disease pathology"},"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>The quantification of phosphorylated tau in biofluids, either cerebrospinal fluid (CSF) or plasma, has shown great promise in detecting Alzheimer\u2019s disease (AD) pathophysiology. Tau phosphorylated at threonine 231 (p-tau231) is one such biomarker in CSF but its usefulness as a blood biomarker is currently unknown. Here, we developed an ultrasensitive Single molecule array (Simoa) for the quantification of plasma p-tau231 which was validated in four independent cohorts (<i>n<\/i>\u2009=\u2009588) in different settings, including the full AD continuum and non-AD neurodegenerative disorders. Plasma p-tau231 was able to identify patients with AD and differentiate them from amyloid-\u03b2 negative cognitively unimpaired (CU) older adults with high accuracy (AUC\u2009=\u20090.92\u20130.94). Plasma p-tau231 also distinguished AD patients from patients with non-AD neurodegenerative disorders (AUC\u2009=\u20090.93), as well as from amyloid-\u03b2 negative MCI patients (AUC\u2009=\u20090.89). In a neuropathology cohort, plasma p-tau231 in samples taken on average 4.2 years prior to post-mortem very accurately identified AD neuropathology in comparison to non-AD neurodegenerative disorders (AUC\u2009=\u20090.99), this is despite all patients being given an AD dementia diagnosis during life. Plasma p-tau231 was highly correlated with CSF p-tau231, tau pathology as assessed by [<sup>18<\/sup>F]MK-6240 positron emission tomography (PET), and brain amyloidosis by [<sup>18<\/sup>F]AZD469 PET. Remarkably, the inflection point of plasma p-tau231, increasing as a function of continuous [<sup>18<\/sup>F]AZD469 amyloid-\u03b2 PET standardized uptake value ratio, was shown to be earlier than standard thresholds of amyloid-\u03b2 PET positivity and the increase of plasma p-tau181. Furthermore, plasma p-tau231 was significantly increased in amyloid-\u03b2 PET quartiles 2\u20134, whereas CSF p-tau217 and plasma p-tau181 increased only at quartiles 3\u20134 and 4, respectively. Finally, plasma p-tau231 differentiated individuals across the entire Braak stage spectrum, including Braak staging from Braak 0 through Braak I\u2013II, which was not observed for plasma p-tau181. To conclude, this novel plasma p-tau231 assay identifies the clinical\u00a0stages of AD\u00a0and neuropathology equally well as plasma p-tau181, but increases earlier, already with subtle amyloid-\u03b2 deposition, prior to the threshold for amyloid-\u03b2 PET positivity has been attained, and also in response to early brain tau deposition. Thus, plasma p-tau231 is a promising novel biomarker of emerging AD pathology with the potential to facilitate clinical trials to identify vulnerable populations below PET threshold of amyloid-\u03b2 positivity or apparent entorhinal tau deposition.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4710","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>Plasma p-tau231: a new biomarker for incipient Alzheimer\u2019s disease pathology - 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\/plasma-p-tau231-a-new-biomarker-for-incipient-alzheimers-disease-pathology-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Plasma p-tau231: a new biomarker for incipient Alzheimer\u2019s disease pathology - 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