Changes in neurodegeneration and amyloid biomarkers in patients with COVID-19 neurological complications and Alzheimer’s disease

Author:

Barros-Aragão Fernanda G. Q.1ORCID,Pinto Talita P.1,Carregari Victor C.1,Rezende Nathane B. S.1,Pinheiro Thaís L.1,Reis-de-Oliveira Guilherme2,Queiroz Daniel C.3,Fonseca Paula L. C.3,Gonçalves Alessandro L.3,Cabral-Castro Mauro J.4,Freitas Gabriel R.1,Vanderborgh Bart1,Sudo Felipe K.1,Mattos Paulo1,Bozza Fernando A.1,Rodrigues Erika C.1,Rodrigues Rosana S.1,Brandão Carlos O.5,Souza Andrea S.1,Aguiar Renato S.3,Martins-de-Souza Daniel2,De Felice Fernanda G.6,Tovar-Moll Fernanda F.1

Affiliation:

1. D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil

2. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP); Campinas, Brazil.

3. Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais; Belo Horizonte, Brazil.

4. Institute of Microbiology Paulo de Goés, Federal University of Rio de Janeiro (UFRJ), Brazil

5. Neurolife Laboratories, Rio de Janeiro, Brazil

6. Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences & Department of Psychiatry, Queen’s University, Kingston; Ontario, Canada.

Abstract

Abstract COVID-19 induces acute and long-term neurological symptoms. Determining the mechanisms underlying acute neurological disease will lead to a better understanding of long-COVID and late-onset outcomes. Here, we investigate in detail a cohort of COVID-19 patients presenting neurological alterations. Clinical and neurological investigation, brain imaging, and bio-sample analyses were carried out. We tested the possibility that COVID-19 shares molecular links with Alzheimer’s disease (AD)-like neurodegeneration by analyzing the framework of ATN (amyloid, pathologic Tau, and neurodegeneration) biomarkers. Altered cerebrospinal fluid (CSF) Tau and amyloid levels in severe COVID-19 patients were comparable to amnestic mild cognitive impairment (aMCI) and AD patients. Increased CSF pro-inflammatory cytokine IL6 and Tau linked systemic inflammation and disease severity to central nervous system alterations. COVID-19 patients presented an altered CSF proteomic pattern, with inflammatory, coagulopathy, and amyloidosis pathways alterations. Collectively, our findings reveal some molecular links between COVID-19 neurological disease and neurodegeneration biomarkers associated with AD.

Publisher

Research Square Platform LLC

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