Meyer, Pierre-François;
Ashton, Nicholas J;
Karikari, Thomas K;
Strikwerda-Brown, Cherie;
Köbe, Theresa;
Gonneaud, Julie;
Pichet Binette, Alexa;
... Presymptomatic Evaluation of Experimental or Novel Treatments fo; + view all
(2022)
Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults.
Annals of Neurology
, 91
(4)
pp. 548-560.
10.1002/ana.26308.
Preview |
Text
Annals of Neurology - 2022 - Meyer.pdf - Accepted Version Download (7MB) | Preview |
Abstract
OBJECTIVE: To evaluate novel plasma p-tau231, p-tau181 as well as Aβ40 and Aβ42 assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults. METHODS: In a cohort of 244 older adults at risk of AD owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231, p-tau181), Aβ40 and Aβ42 with immunoprecipitation mass spectrometry, and Simoa NfL. A subset of 129 participants underwent amyloid-β (18 F-NAV4694) and tau (18 F-flortaucipir) PET assessments. We investigated plasma biomarker associations with Aβ and tau PET at the global and voxel level and tested plasma biomarker combinations for improved detection of Aβ-PET positivity. We also investigated associations with 8-year cognitive change. RESULTS: Plasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma Aβ42/40 explained more variance in global Aβ-PET binding than Aβ42 alone. P-tau231 also showed strong and widespread associations with cortical Aβ-PET binding. Combining Aβ42/40 with p-tau231 or p-tau181 allowed for good distinction between Aβ-negative and -positive participants (AUC range 0.81-0.86). Individuals with low plasma Aβ42/40 and high p-tau experienced faster cognitive decline. INTERPRETATION: Plasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in pre-symptomatic individuals. The combination of p-tau and Aβ42/40 biomarkers detected early AD pathology and cognitive decline. Such markers could be used as pre-screening tools to reduce the cost of prevention trials. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ana.26308 |
| Publisher version: | https://doi.org/10.1002/ana.26308 |
| 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: | Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) Research Group |
| UCL classification: | 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 > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10143241 |
Archive Staff Only
 |
View Item |
