SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology

Shen, W.-B.; Logue, J.; Yang, P.; Baracco, L.; Elahi, M.; Reece, E. A.; Wang, B.; Li, L.; Blanchard, T.; Han, Z.; Frieman, M.; Rissman, R. A.

doi:10.1101/2022.01.31.478476

bioRxiv · 10.1101/2022.01.31.478476

SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology

Shen, W.-B.·Logue, J.·Yang, P.·Baracco, L.·Elahi, M.·Reece, E. A.·Wang, B.·Li, L.·Blanchard, T.·Han, Z.·Frieman, M.·Rissman, R. A.

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Abstract

Major cell entry factors of SARS-CoV-2 are present in neurons; however, the neurotropism of SARS-CoV-2 and the phenotypes of infected neurons are still unclear. Acute neurological disorders occur in many patients, and one-third of COVID-19 survivors suffer from "brain diseases". Here, we show that SARS-CoV-2 invades the brains of five patients with COVID-19 and Alzheimers, autism, frontotemporal dementia or no underlying condition by infecting neurons and other cells in the cortex. SARS-CoV-2 induces or enhances Alzheimers-like neuropathology with manifestations of {beta}-amyloid aggregation and plaque formation, tauopathy, neuroinflammation and cell death. SARS-CoV-2 infects mature but not immature neurons derived from inducible pluripotent stem cells from healthy and Alzheimers individuals through its receptor ACE2 and facilitator neuropilin-1. SARS-CoV-2 triggers Alzheimers-like gene programs in healthy neurons and exacerbates Alzheimers neuropathology. A gene signature defined as an Alzheimers infectious etiology is identified through SARS-CoV-2 infection, and silencing the top three downregulated genes in human primary neurons recapitulates the neurodegenerative phenotypes of SARS-CoV-2. Thus, SARS-CoV-2 invades the brain and activates an Alzheimers-like program.

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Shen, W.-B., Logue, J., Yang, P., Baracco, L., Elahi, M., Reece, E. A., Wang, B., Li, L., Blanchard, T., Han, Z., Frieman, M., Rissman, R. A.. 2022-02-01. SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology. https://doi.org/10.1101/2022.01.31.478476

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