Alzheimer's‐like signaling in brains of COVID‐19 patients
Open Access
- 3 February 2022
- journal article
- research article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 18 (5), 955-965
- https://doi.org/10.1002/alz.12558
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 co-immunoprecipitation/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.This publication has 63 references indexed in Scilit:
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