articleNature MedicineMar 6, 2025HYBRID OA

Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease

Northwestern University · Agency for Science, Technology and Research · +5 more institutions

PubMed
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Abstract

Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ clearance. Using high-resolution spatial transcriptomics alongside single-cell RNA sequencing, we delve deeper into the transcriptional pathways involved in Aβ removal after lecanemab treatment. We uncover spatially distinct…

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91
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Authors

23

Topics & keywords

Keywords
  • Disease
  • Amyloid (mycology)
  • Amyloid β
  • Medicine
  • Alzheimer's disease
  • Microglia
  • Immunology
  • Neuroscience
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