Usefulness of a blood-based test of phosphorylated tau 181 was evaluate in order to see whether the biomarker a) can differentiate Alzheimer’s disease dementia from no cognitive impairment, mild cognitive impairment (MCI) due to Alzheimer’s disease, and other neurodegenerative diseases; b) reflects abnormalities in tau or amyloid PET scans and c) predicts future cognitive decline and hippocampal atrophy. Authors tested the feasibility of using the assay in a primary care cohort, that included controls without a diagnosis of a neurological condition and patients referred from primary care physicians for specialist care at the McGill University Research Centre for Studies in Aging. This assay proved to be sensitive in measuring brain derived p-tau181. Plasma p-tau181 provided high diagnostic accuracy in discriminating amyloid β-positive cognitively unimpaired older adults and amyloid β-positive individuals with MCI from amyloid β-negative cognitively unimpaired older adults and young adults. The test performed well in identifying clinically diagnosed Alzheimer’s disease patients with unknown brain amyloid status and in differentiation of Alzheimer’s disease from other neurodegenerative diseases. The strong correlation between plasma p-tau181 and amyloid β PET, together with the increased plasma p-tau181 in amyloid β PET-positive and tau PET-negative individuals suggests that test detects Alzheimer’s disease type pathology in the very early disease stages. Additionally, blood p-tau 181 predicted cognitive decline and hippocampal atrophy over a period of 1 year. This high-performance blood p-tau181 assay could represent the first simple, practical and scalable test for the diagnosis of Alzheimer’s disease.
Thomas K Karikari*, Tharick A Pascoal*, Nicholas J Ashton, Shorena Janelidze, Andréa Lessa Benedet, Juan Lantero Rodriguez, Mira Chamoun, Melissa Savard, Min Su Kang, Joseph Therriault, Michael Schöll, Gassan Massarweh, Jean-Paul Soucy, Kina Höglund, Gunnar Brinkmalm, Niklas Mattsson, Sebastian Palmqvist, Serge Gauthier, Erik Stomrud, Henrik Zetterberg, Oskar Hansson†, Pedro Rosa-Neto†, Kaj Blennow †. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020 May;19(5):422-433. doi: 10.1016/S1474-4422(20)30071-5.https://pubmed.ncbi.nlm.nih.gov/32333900/