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Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease

Chen, Z; Mengel, D; Keshavan, A; Rissman, RA; Billinton, A; Perkinton, M; Percival-Alwyn, J; ... Walsh, DM; + view all (2019) Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease. Alzheimer's & Dementia , 15 (3) pp. 487-496. 10.1016/j.jalz.2018.09.010. Green open access

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Abstract

INTRODUCTION: The tau protein plays a central role in Alzheimer's disease (AD), and there is huge interest in measuring tau in blood and cerebrospinal fluid (CSF). METHODS: We developed a set of immunoassays to measure tau in specimens from humans diagnosed based on current best clinical and CSF biomarker criteria. RESULTS: In CSF, mid-region- and N-terminal-detected tau predominated and rose in disease. In plasma, an N-terminal assay (NT1) detected elevated levels of tau in AD and AD-mild cognitive impairment (MCI). Plasma NT1 measurements separated controls from AD-MCI (area under the curve [AUC] = 0.88) and AD (AUC = 0.96) in a discovery cohort and in a Validation Cohort (with AUCs = 0.79 and 0.75, respectively). DISCUSSION: The forms of tau in CSF and plasma are distinct, but in each specimen type, the levels of certain fragments are increased in AD. Measurement of plasma NT1 tau should be aggressively pursued as a potential blood-based screening test for AD/AD-MCI.

Type: Article
Title: Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jalz.2018.09.010
Publisher version: https://doi.org/10.1016/j.jalz.2018.09.010
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Biomarker, Dementia, Enzyme-linked immunoassay, Mild cognitive impairment, Plasma, Single molecule array
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10063656
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