Background: Recent advances in Alzheimer's disease (AD) therapeutics involve immunization against amyloid-β (Aβ). Post-mortem brain analysis from the first active Aβ immunotherapy trial indicated clearance of Aβ in some AD patients. Yet, the mechanisms regulating Aβ clearance following immunization remain unknown.
Method: Here, we utilized a novel spatial proteogenomics approach to study brain tissues from 13 AD patients immunized with Aβ. We compared these actively immunized patient brains to tissues from non-immunized AD patients and non-neurologic disease controls. Additionally, we used spatial proteogenomics and single-cell RNA sequencing technologies to investigate the effects of lecanemab, a passive anti-Aβ drug.
Result: We reveal the transcriptomic neuroimmune response in the Aβ plaque microenvironment following anti-Aβ immunization. This response is characterized by an increase in genes associated with the TREM2-APOE axis in microglia of the immunized AD cortex.
Conclusion: Altogether, our data uncover immediate and lasting neuroimmune responses in the AD brain induced by active and passive Aβ vaccination.
© 2024 The Alzheimer's Association. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.