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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.

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