Amyloid processing in COVID-19-associated neurological syndromes
© 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry..
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:161 |
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| Enthalten in: |
Journal of neurochemistry - 161(2022), 2 vom: 08. Apr., Seite 146-157 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ziff, Oliver J [VerfasserIn] |
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| Links: |
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| Themen: |
APP |
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| Anmerkungen: |
Date Completed 22.04.2022 Date Revised 16.02.2024 published: Print-Electronic ErratumIn: J Neurochem. 2023 Jul;166(1):e1. - PMID 37414438 Citation Status MEDLINE |
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| doi: |
10.1111/jnc.15585 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 500 | |a ErratumIn: J Neurochem. 2023 Jul;166(1):e1. - PMID 37414438 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a APP | |
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a amyloid processing | |
| 650 | 4 | |a beta amyloid | |
| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
| 650 | 7 | |a Amyloid beta-Protein Precursor |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 700 | 1 | |a Ashton, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Puja R |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Athauda, Dilan |e verfasserin |4 aut | |
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| 700 | 1 | |a Houlihan, Catherine F |e verfasserin |4 aut | |
| 700 | 1 | |a Gauthier, Serge |e verfasserin |4 aut | |
| 700 | 1 | |a Rosa-Neto, Pedro |e verfasserin |4 aut | |
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| 700 | 1 | |a Zetterberg, Henrik |e verfasserin |4 aut | |
| 700 | 1 | |a Benjamin, Laura A |e verfasserin |4 aut | |
| 700 | 1 | |a Paterson, Ross W |e verfasserin |4 aut | |
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