SARS-CoV-2 induces Alzheimer’s disease–related amyloid-β pathology in ex vivo human retinal explants and retinal organoids
- Sean J. Miller
- Rahul M. Dhodapkar
- Hande Eda Sutova
- Yao Xue
- Seunghoon Lee
- Robert Logan
- Chongzhao Ran
- Sagar Bhatta
- Ashley Gomm
- In Gyoung Ju
- Michael Heyang
- Rayyan Y. Darji
- Marcello Distasio
- Rudolph E. Tanzi
- Can Zhang
- Z. Jimmy Zhou
- Brian P. Hafler
2025-07-04
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.