Amyloid processing in COVID-19-associated neurological syndromes.

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 × 10-8 ), Aβ42 (p = 3.5 × 10-7 ), 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 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.

• Authors: Oliver J Ziff, Nicholas J Ashton, Puja R Mehta, Rachel Brown, Dilan Athauda, Judith Heaney, Amanda J Heslegrave, Andrea Lessa Benedet, Kaj Blennow, Anna M Checkley, Catherine F Houlihan, Serge Gauthier, Pedro Rosa-Neto, Nick C Fox, Jonathan M Schott, Henrik Zetterberg, Laura A Benjamin, Ross W Paterson
• Journal: Journal of neurochemistry (J Neurochem) Vol. 161 Issue 2 Pg. 146-157 (04 2022) ISSN: 1471-4159 [Electronic] England
• PMID: 35137414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Biomarkers

Topics

• Alzheimer Disease (cerebrospinal fluid)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (cerebrospinal fluid)
• Amyloidosis
• Biomarkers (cerebrospinal fluid)
• COVID-19 (complications)
• Cohort Studies
• Cross-Sectional Studies
• Humans
• Pilot Projects
• Prospective Studies
• SARS-CoV-2