Alzheimer's‐like signaling in brains of COVID‐19 patients

Abstract

Introduction:The mechanisms that lead to cognitive impairment associated with COVID-19 are not well understood.Methods: Brain lysates from control and COVID-19 patients were analyzed for oxidative stress and inflammatory signaling pathway markers, and measurements of Alzheimer's disease (AD)-linked signaling biochemistry. Post-translational modifications of the ryanodine receptor/calcium (Ca2 + ) release channels (RyR) on the endoplasmic reticuli (ER), known to be linked to AD, were also measured by coimmunoprecipitation/immunoblotting of the brain lysates. Results:We provide evidence linking SARS-CoV-2 infection to activation of TGF-β signaling and oxidative overload. The neuropathological pathways causing tau hyperphosphorylation typically associated with AD were also shown to be activated in COVID-19 patients. RyR2 in COVID-19 brains demonstrated a "leaky" phenotype, which can promote cognitive and behavioral defects.Discussion: COVID-19 neuropathology includes AD-like features and leaky RyR2 channels could be a therapeutic target for amelioration of some cognitive defects associated with SARS-CoV-2 infection and long COVID.

Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model

“…Further very recent studies corroborate our arguments. Analyses of brain lysates from COVID-19 patients revealed increased markers of inflammation and oxidative stress as well as activation of pathways causing tau hyper-phosphorylation typically associated with Alzheimer´s disease, in the absence of virus in the brain 62 Patients with neurological impairment due to COVID-19 showed significantly elevated plasma levels of t-tau, p-tau181, and other biomarkers relevant to Alzheimer´s disease, correlating with the severity of COVID-19 and age 63 Increased levels of such blood neuronal markers at admission are associated with death due to COVID-19, with tau being the strongest predictor of mortality. 64 Patients with neurological symptoms persisting 1 to 3 months post COVID-19 infection showed increase of proteins related to neurodegenerative diseases (amyloid beta, neurofilament light chain, total tau, and p-tau181) in neuronal-enriched extracellular vesicle (nEV) pointing towards ongoing neurodegenerative processes.…”

COVID-19 in the perioperative setting: A review of the literature and the clinical landscape

“…Neurocognitive dysfunction and damage after COVID infection are also common. 31 , 32 , 33 , 34 , 35 , 36 Delirium is a well-recognized complication of COVID and is associated with a poor prognosis and increased mortality. While specific post-COVID perioperative neurocognitive complications are not yet reported, we remain highly concerned about the risk of postoperative delirium and other postoperative neurocognitive disorders.…”

Peptide from NSP7 is able to form amyloid-like fibrils: artifact or challenge to drug design?

“…The peptide can be delivered to cells using carriers or in the form of RNA encoding it [10], which has the elements necessary for translation on the eukaryotic ribosome. At the same time, it must be kept in mind that the effect of amyloid-like viral structures on the body has not been studied enough [11], [12] however, for example, in the case of the influenza virus, the formation of amyloid-like fibrils by the PB1-F2 protein during the life cycle of the virus does not have a significant effect on the host organism [13]- [16].…”