Ziff, Oliver J;
Ashton, Nicholas J;
Mehta, Puja R;
Brown, Rachel;
Athauda, Dilan;
Heaney, Judith;
Heslegrave, Amanda J;
... Paterson, Ross W; + view all
(2022)
Amyloid processing in COVID-19-associated neurological syndromes.
Journal of Neurochemistry
, 161
(2)
pp. 146-157.
10.1111/jnc.15585.
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Abstract
SARS-CoV-2 infection can damage the nervous system with multiple neurological manifestations described. However, there is limited understanding of the mechanisms underlying COVID-19 neurological injury. This is a cross-sectional exploratory prospective biomarker cohort study of 21 patients with COVID-19 neurological syndromes (Guillain Barre Syndrome [GBS], encephalitis, encephalopathy, acute disseminated encephalomyelitis [ADEM], intracranial hypertension and central pain syndrome) and 23 healthy COVID-19 negative controls. We measured cerebrospinal fluid (CSF) and serum biomarkers of amyloid processing, neuronal injury (neurofilament light), astrocyte activation (GFAp) and neuroinflammation (tissue necrosis factor [TNF] ɑ, interleukin [IL]-6, IL-1β, IL-8). Patients with COVID-19 neurological syndromes had significantly reduced CSF soluble amyloid precursor protein (sAPP)-ɑ (p = 0.004) and sAPPβ (p = 0.03) as well as amyloid β (Aβ) 40 (p = 5.2x10-8 ), Aβ42 (p = 3.5x10-7 ) and Aβ42/Aβ40 ratio (p = 0.005) compared to controls. Patients with COVID-19 neurological syndromes showed significantly increased neurofilament light (NfL, p = 0.001) and this negatively correlated with sAPPɑ and sAPPβ. Conversely, GFAp was significantly reduced in COVID-19 neurological syndromes (p = 0.0001) and this positively correlated with sAPPɑ and sAPPβ. COVID-19 neurological patients also displayed significantly increased CSF proinflammatory cytokines and these negatively correlated with sAPPɑ and sAPPβ. A sensitivity analysis of COVID-19 associated GBS revealed a non-significant trend towards greater impairment of amyloid processing in COVID-19 central than peripheral neurological syndromes. This pilot study raises the possibility that patients with COVID-19 associated neurological syndromes exhibit impaired amyloid processing. Altered amyloid processing was linked to neuronal injury and neuroinflammation but reduced astrocyte activation.
| Type: | Article |
|---|---|
| Title: | Amyloid processing in COVID-19-associated neurological syndromes |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/jnc.15585 |
| Publisher version: | http://doi.org/10.1111/jnc.15585 |
| Language: | English |
| Additional information: | Copyright © 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), 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. |
| Keywords: | APP, Alzheimer's disease, COVID-19, amyloid processing, beta amyloid |
| 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/10143512 |
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