tetano
Editor, Senior Moderator
Sci Adv
. 2025 Jul 4;11(27):eads5006.
doi: 10.1126/sciadv.ads5006. Epub 2025 Jul 4. SARS-CoV-2 induces Alzheimer's disease-related amyloid-β pathology in ex vivo human retinal explants and retinal organoids
Sean J Miller[SUP] 1 [/SUP], Rahul M Dhodapkar[SUP] 1 [/SUP], Hande Eda Sutova[SUP] 1 [/SUP], Yao Xue[SUP] 1 [/SUP], Seunghoon Lee[SUP] 1 [/SUP], Robert Logan[SUP] 2 [/SUP], Chongzhao Ran[SUP] 3 [/SUP], Sagar Bhatta[SUP] 1 [/SUP], Ashley Gomm[SUP] 4 [/SUP], In Gyoung Ju[SUP] 1 [/SUP], Michael Heyang[SUP] 1 [/SUP], Rayyan Y Darji[SUP] 1 [/SUP], Marcello DiStasio[SUP] 1 5 [/SUP], Rudolph E Tanzi[SUP] 4 [/SUP], Can Zhang[SUP] 4 [/SUP], Z Jimmy Zhou[SUP] 1 [/SUP], Brian P Hafler[SUP] 1 5 6 [/SUP]
Affiliations
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.
. 2025 Jul 4;11(27):eads5006.
doi: 10.1126/sciadv.ads5006. Epub 2025 Jul 4. SARS-CoV-2 induces Alzheimer's disease-related amyloid-β pathology in ex vivo human retinal explants and retinal organoids
Sean J Miller[SUP] 1 [/SUP], Rahul M Dhodapkar[SUP] 1 [/SUP], Hande Eda Sutova[SUP] 1 [/SUP], Yao Xue[SUP] 1 [/SUP], Seunghoon Lee[SUP] 1 [/SUP], Robert Logan[SUP] 2 [/SUP], Chongzhao Ran[SUP] 3 [/SUP], Sagar Bhatta[SUP] 1 [/SUP], Ashley Gomm[SUP] 4 [/SUP], In Gyoung Ju[SUP] 1 [/SUP], Michael Heyang[SUP] 1 [/SUP], Rayyan Y Darji[SUP] 1 [/SUP], Marcello DiStasio[SUP] 1 5 [/SUP], Rudolph E Tanzi[SUP] 4 [/SUP], Can Zhang[SUP] 4 [/SUP], Z Jimmy Zhou[SUP] 1 [/SUP], Brian P Hafler[SUP] 1 5 6 [/SUP]
Affiliations
- PMID: 40614201
- PMCID: PMC12227045
- DOI: 10.1126/sciadv.ads5006
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.