Salvadó, G;
Milà-Alomà, M;
Shekari, M;
Minguillon, C;
Fauria, K;
Niñerola-Baizán, A;
Perissinotti, A;
... Gispert, JD; + view all
(2021)
Cerebral amyloid‐β load is associated with neurodegeneration and gliosis: Mediation by p‐tau and interactions with risk factors early in the Alzheimer's continuum.
Alzheimer's & Dementia
, 17
(5)
pp. 788-800.
10.1002/alz.12245.
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Abstract
Introduction: The association between cerebral amyloid‐β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. / Methods: In 318 cognitively unimpaired participants, we assessed the association between amyloid‐β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE‐ε4), and the mediation effect of tau and neurodegeneration were also investigated. / Results: Centiloids were positively associated with CSF biomarkers of tau pathology (p‐tau), neurodegeneration (t‐tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL‐40, GFAP, sTREM2), presenting interactions with age (p‐tau, t‐tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p‐tau, except for NfL. The interaction between sex and amyloid‐β on sTREM2 and NfL was also tau‐independent. / Discussion: Early amyloid‐β accumulation has a tau‐independent effect on neurodegeneration and a tau‐dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau.
| Type: | Article |
|---|---|
| Title: | Cerebral amyloid‐β load is associated with neurodegeneration and gliosis: Mediation by p‐tau and interactions with risk factors early in the Alzheimer's continuum |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12245 |
| Publisher version: | https://doi.org/10.1002/alz.12245 |
| Language: | English |
| Additional information: | Copyright © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | [18F]flutemetamol, Alzheimer, biomarkers, glial activation, inflammation, modulation, neuronal injury, 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-pp.ucl.ac.uk/id/eprint/10124219 |
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