Ashton, Nicholas J;
Benedet, Andréa L;
Pascoal, Tharick A;
Karikari, Thomas K;
Lantero-Rodriguez, Juan;
Brum, Wagner S;
Mathotaarachchi, Sulantha;
... Rosa-Neto, Pedro; + view all
(2022)
Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease.
EBioMedicine
, 76
, Article 103836. 10.1016/j.ebiom.2022.103836.
Preview |
PDF
Zetterberg_1-s2.0-S2352396422000202-main.pdf - Published Version Download (1MB) | Preview |
Abstract
BACKGROUND: Phosphorylated tau (p-tau) epitopes in cerebrospinal fluid (CSF) are accurate biomarkers for a pathological and clinical diagnosis of Alzheimer's disease (AD) and are seen to be increased in preclinical stage of the disease. However, it is unknown if these increases transpire earlier, prior to amyloid-beta (Aβ) positivity as determined by position emission tomography (PET), and if an ordinal sequence of p-tau epitopes occurs at this incipient phase METHODS: We measured CSF concentrations of p-tau181, p-tau217 and p-tau231 in 171 participants across the AD continuum who had undergone Aβ ([18F]AZD4694) and tau ([18F]MK6240) position emission tomography (PET) and clinical assessment FINDINGS: All CSF p-tau biomarkers were accurate predictors of cognitive impairment but CSF p-tau217 demonstrated the largest fold-changes in AD patients in comparison to non-AD dementias and cognitively unimpaired individuals. CSF p-tau231 and p-tau217 predicted Aβ and tau to a similar degree but p-tau231 attained abnormal levels first. P-tau231 was sensitive to the earliest changes of Aβ in the medial orbitofrontal, precuneus and posterior cingulate before global Aβ PET positivity was reached INTERPRETATION: We demonstrate that CSF p-tau231 increases early in development of AD pathology and is a principal candidate for detecting incipient Aβ pathology for therapeutic trial application FUNDING: Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Weston Brain Institute, Brain Canada Foundation, the Fonds de Recherche du Québec.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2022.103836 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2022.103836 |
| Language: | English |
| Additional information: | ©2022 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | Alzheimer's disease, Amyloid, Cerebrospinal fluid, Phosphorylated tau, Positron emission tomography, Preclinical |
| 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/10144098 |
Archive Staff Only
 |
View Item |
