{"id":4609,"date":"2020-07-24T12:47:19","date_gmt":"2020-07-24T16:47:19","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/18f-mk-6240-pet-for-early-and-late-detection-of-neurofibrillary-tangles-2\/"},"modified":"2024-12-03T14:57:09","modified_gmt":"2024-12-03T19:57:09","slug":"18f-mk-6240-pet-for-early-and-late-detection-of-neurofibrillary-tangles-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/18f-mk-6240-pet-for-early-and-late-detection-of-neurofibrillary-tangles-2\/","title":{"rendered":"18F-MK-6240 PET for early and late detection of neurofibrillary tangles"},"content":{"rendered":"<h2 id=\"205587325\" class=\"abstract-title\">Abstract<\/h2>\n<section class=\"abstract\">\n<p class=\"chapter-para\">Braak stages of tau neurofibrillary tangle accumulation have been incorporated in the criteria for the neuropathological diagnosis of Alzheimer\u2019s disease. It is expected that Braak staging using brain imaging can stratify living individuals according to their individual patterns of tau deposition, which may prove crucial for clinical trials and practice. However, previous studies using the first-generation tau PET agents have shown a low sensitivity to detect tau pathology in areas corresponding to early Braak histopathological stages (\u223c20% of cognitively unimpaired elderly with tau deposition in regions corresponding to Braak I\u2013II), in contrast to \u223c80\u201390% reported in post-mortem cohorts. Here, we tested whether the novel high affinity tau tangles tracer\u00a0<sup>18<\/sup>F-MK-6240 can better identify individuals in the early stages of tau accumulation. To this end, we studied 301 individuals (30 cognitively unimpaired young, 138 cognitively unimpaired elderly, 67 with mild cognitive impairment, 54 with Alzheimer\u2019s disease dementia, and 12 with frontotemporal dementia) with amyloid-\u03b2\u00a0<sup>18<\/sup>F-NAV4694, tau\u00a0<sup>18<\/sup>F-MK-6240, MRI, and clinical assessments.\u00a0<sup>18<\/sup>F-MK-6240 standardized uptake value ratio images were acquired at 90\u2013110 min after the tracer injection.\u00a0<sup>18<\/sup>F-MK-6240 discriminated Alzheimer\u2019s disease dementia from mild cognitive impairment and frontotemporal dementia with high accuracy (\u223c85\u2013100%).\u00a0<sup>18<\/sup>F-MK-6240 recapitulated topographical patterns consistent with the six hierarchical stages proposed by Braak in 98% of our population. Cognition and amyloid-\u03b2 status explained most of the Braak stages variance (<em>P\u2009<\/em>&lt;<em>\u2009<\/em>0.0001, R<sup>2<\/sup>\u00a0= 0.75). No single region of interest standardized uptake value ratio accurately segregated individuals into the six topographic Braak stages. Sixty-eight per cent of the cognitively unimpaired elderly amyloid-\u03b2-positive and 37% of the cognitively unimpaired elderly amyloid-\u03b2-negative subjects displayed tau deposition, at least in the transentorhinal cortex (Braak I). Tau deposition solely in the transentorhinal cortex was associated with an elevated prevalence of amyloid-\u03b2, neurodegeneration, and cognitive impairment (<em>P\u2009<\/em>&lt;<em>\u2009<\/em>0.0001).\u00a0<sup>18<\/sup>F-MK-6240 deposition in regions corresponding to Braak IV\u2013VI was associated with the highest prevalence of neurodegeneration, whereas in Braak V\u2013VI regions with the highest prevalence of cognitive impairment. Our results suggest that the hierarchical six-stage Braak model using\u00a0<sup>18<\/sup>F-MK-6240 imaging provides an index of early and late tau accumulation as well as disease stage in preclinical and symptomatic individuals. Tau PET Braak staging using high affinity tracers has the potential to be incorporated in the diagnosis of living patients with Alzheimer\u2019s disease in the near future.<\/p>\n<\/section>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4609","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>18F-MK-6240 PET for early and late detection of neurofibrillary tangles - 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\/18f-mk-6240-pet-for-early-and-late-detection-of-neurofibrillary-tangles-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"18F-MK-6240 PET for early and late detection of neurofibrillary tangles - 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