New research strengthens the hypothesis that immune responses to central nervous system infections trigger amyloid-beta (Aβ) clumping. The work uses SARS-CoV-2 infection of human retinal tissue and retinal organoids as a model to investigate the potential antimicrobial origins of Alzheimer’s disease (AD). Research has implicated Aβ as a contributor to AD; an emergent theory suggests that the innate immune system produces aggregating Aβ to ensnare pathogens in the central nervous system – and that this pathway, over time and with repeat infections, could drive AD. Sean Miller and colleagues investigated this hypothesis by compiling tissue from 20 postmortem eyes from patients with AD to characterize Aβ accumulation. They then grew human retinal organoids based on stem cells from those tissues and exposed them to SARS-CoV-2. Miller et al. also evaluated postmortem eyes from patients with SARS-CoV-2 but without a history of AD. Ultimately, the analyses connected SARS-CoV-2 infection with immune cell-based Aβ extracellular clumping. Next, Miller et al. investigated whether preventing SARS-CoV-2 infection pharmacologically would preclude Spike 1 protein-mediated Aβ clustering. They did this by blocking the interaction between SARS-CoV-2 and the Neuropilin-1 protein, a recently recognized co-receptor for SARS-CoV-2 entry. Blocking the interaction reduced Aβ clustering in the human retinal tissue. “The accumulation of amyloid-β may be associated with the cognitive symptoms associated with COVID-19 and suggest that NRP1 inhibitors or antiviral medications may serve as therapeutic tools to prevent these consequences,” the authors write.

 

 

For reporters interested in the intersection of microbes, antimicrobial responses, and neurodegenerative amyloids, a 2025 Science Advances paper discovered that a protein from a pathogenic bacterium blocks amyloid proteins from aggregating: https://www.science.org/doi/10.1126/sciadv.ads7525

The research team led by Nobel Laureates May-Britt and Edvard Moser at the Norwegian University of Science and Technology (NTNU) is already known for their discovery of the brain’s sense of place. Now they have shown that the brain also weaves a tapestry of time: The brain segments and organizes events into experiences, placing unique bookmarks on them so that our lives don’t become a blurry stream, but rather a series of meaningful moments and memories we can revisit and learn from.

Resarchers in the UK Dementia Research Institute at Cardiff University, UK, have now generated the first large-scale stem cell bank from over 100 individuals Reelected for extremes of AD PRS, which had previously been determined by genome sequencing. The results of the work are published today in Stem Cell Reports. About two thirds of the donors had been diagnosed with AD and had a relatively high PRS while one third were cognitively healthy, age-matched individuals with a low PRS. Blood cells from these individuals were genetically engineered to turn them into induced pluripotent stem cells (iPSCs), which are immature cells capable of generating all cell types of the body.