18F-MK-6240 PET for early and late detection of neurofibrillary tangles

AbstractBraak stages of tau neurofibrillary tangle accumulation have been incorporated in the criteria for the neuropathological diagnosis of Alzheimer ’s 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 (∼20% of cognitively unimpaired elderly with tau deposition in regions corresponding to Braak I–II), in contrast to ∼80–90% reported in post-mortem cohorts. Here, we tested whether the novel h igh affinity tau tangles tracer18F-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 ’s disease dementia, and 12 with frontotemporal dementia) with amyloid-β18F-NAV4694, tau18F-MK-6240, MRI, and clinical assessments.18F-MK-6240 standardized uptake value ratio images were acquired at 90 –110 min after the tracer injection.18F-MK-6240 discriminated Alzheimer ’s disease dementia from mild cognitive impairment and frontotemporal dementia with high accuracy (∼85–100%).18F-MK-6240 recapitulated topographical patterns consistent with the six h...

Source: Brain - July 16, 2020 Category: Neurology Source Type: research