Elixir Associates转å‘了
???? Why do some Alzheimer’s immunotherapies work better than others? A new study offers answers—down to the microglial gene signature. In a study only just published in Nature Magazine (Nature Medicine), David Gate and collaborators from Northwestern University apply high-resolution spatial transcriptomics, single-cell RNA-seq, and proteogenomics to decode the immune response to amyloid-β (Aβ) immunotherapies—both active (AN1792 vaccine) and passive (lecanemab)—in Alzheimer’s disease (AD) brains. ?? Key findings ?? ??Both types of Aβ immunization trigger region and cell-type-specific microglial states, particularly at Aβ-rich “niches.†??Microglial upregulation of TREM2, APOE, A2M, and MARCKS correlates with effective Aβ clearance. ??Complement signaling and IL-2–STAT5 pathways are central to immune activity at these sites. ??Distinct microglial signatures differentiate brains with extensive vs. limited Aβ clearance—even within the same treatment group. ??In lecanemab-treated patients, SPP1 and APOC1 mark active plaque-engulfing microglia. ?? Perhaps most intriguingly, the data show that microglial states can shift toward a homeostatic profile resembling healthy brains—but only under certain immunization outcomes. This could inform next-gen AD immunotherapies! Full Article: https://lnkd.in/etgkUHgZ #Neuroscience #AlzheimersDisease #Neuroimmunology #Microglia #SpatialTranscriptomics #Neurodegeneration #Aduhelm #Lecanemab #TREM2 #Immunotherapy #Neurobiology #BrainHealth #Biotech