Amyloid processing in COVID-19-associated neurological syndromes



Ziff, Oliver J, Ashton, Nicholas J, Mehta, Puja R, Brown, Rachel, Athauda, Dilan, Heaney, Judith, Heslegrave, Amanda J, Benedet, Andrea Lessa, Blennow, Kaj, Checkley, Anna M
et al (show 8 more authors) (2022) Amyloid processing in COVID-19-associated neurological syndromes. JOURNAL OF NEUROCHEMISTRY, 161 (2). pp. 146-157.

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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 = 5.2 × 10<sup>-8</sup> ), Aβ42 (p = 3.5 × 10<sup>-7</sup> ), 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 toward 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.

Item Type: Article
Uncontrolled Keywords: Alzheimer's disease, amyloid processing, APP, beta amyloid, COVID-19
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 03 May 2022 15:32
Last Modified: 18 Jan 2023 21:04
DOI: 10.1111/jnc.15585
Open Access URL: https://onlinelibrary.wiley.com/doi/10.1111/jnc.15...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3154232