Amyloid processing in COVID-19-associated neurological syndromes.
J Neurochem
; 161(2): 146-157, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35137414
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] É, interleukin [IL]-6, IL-1ß, IL-8). Patients with COVID-19 neurological syndromes had significantly reduced CSF soluble amyloid precursor protein (sAPP)-É (p = 0.004) and sAPPß (p = 0.03) as well as amyloid ß (Aß) 40 (p = 5.2 × 10-8 ), Aß42 (p = 3.5 × 10-7 ), and Aß42/Aß40 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 sAPPÉ and sAPPß. Conversely, GFAp was significantly reduced in COVID-19 neurological syndromes (p = 0.0001) and this positively correlated with sAPPÉ and sAPPß. COVID-19 neurological patients also displayed significantly increased CSF proinflammatory cytokines and these negatively correlated with sAPPÉ and sAPPß. 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
COVID-19
/
Amiloidose
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article