Publication date: Jul 04, 2025
While the etiology of Alzheimer’s disease remains unknown, there is growing support for the amyloid-β antimicrobial hypothesis. Amyloid-β, the main component of amyloid plaques in Alzheimer’s disease, has been shown to be generated in the presence of microbes. Entrapment of microbes by aggregated amyloid-β may serve as an innate immune response to pathogenic infections. To understand the association of amyloid-β plaques and pathogenic infections in the central nervous system, we obtained viable short-interval postmortem human retinal tissue and generated human retinal organoids that contain electrophysiologically active neurons. Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces amyloid-β extracellular protein aggregates in human retinal explants and retinal organoids. Last, pharmacological inhibition of neuropilin-1 resulted in reduced amyloid-β deposition in human retinal explants treated with SARS-CoV-2 Spike 1 protein. These results suggest that Spike 1 protein, during infection with SARS-CoV-2, can induce amyloid-β aggregation, which may be associated with the neurological symptoms experienced in COVID-19.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Alzheimer’s disease |
| disease | MESH | etiology |
| disease | MESH | amyloid plaques |
| disease | IDO | innate immune response |
| disease | MESH | infections |
| disease | IDO | protein |
| disease | IDO | infection |
| disease | MESH | COVID-19 |
| disease | MESH | dementia |
| disease | IDO | production |
| disease | IDO | bacteria |
| disease | MESH | fungal infections |
| disease | MESH | viral infection |
| disease | MESH | cytokine storm |
| pathway | REACTOME | Antimicrobial peptides |
| disease | MESH | memory loss |
| disease | MESH | Neurodegenerative Disease |
| drug | DRUGBANK | Trestolone |
| pathway | KEGG | Alzheimer disease |