Milà-Alomà, M;
Salvadó, G;
Gispert, JD;
Vilor-Tejedor, N;
Grau-Rivera, O;
Sala-Vila, A;
Sánchez-Benavides, G;
... ALFA study; + view all
(2020)
Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum.
Alzheimer's & Dementia
10.1002/alz.12131.
(In press).
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Abstract
Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid‐β (Aβ)42, Aβ40, phosphorylated tau (p‐tau), total tau (t‐tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α‐synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum . Results: CSF t‐tau, p‐tau, and neurogranin increase throughout aging only in Aβ‐positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p‐tau and p‐tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p‐tau; t‐tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Discussion: Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum .
| Type: | Article |
|---|---|
| Title: | Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12131 |
| Publisher version: | https://doi.org/10.1002/alz.12131 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Keywords: | Alzheimer's disease, biomarker, neurodegeneration, neuroinflammation, preclinical |
| 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/10103828 |
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