SARS-CoV-2 induces Alzheimer’s disease–related amyloid-β pathology in ex vivo human retinal explants and retinal organoids

作者：Sean Miller, Rahul M. Dhodapkar, Hande Eda Sutova, Xue Yao, 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, Zhishang Zhou, Brian P. Hafler · 发表于：Science Advances · 年份：2025 · DOI：10.1126/sciadv.ads5006 · 被引用次数：11 · 研究领域：Retinal and Optic Conditions、Long-Term Effects of COVID-19、Retinal Imaging and Analysis

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.