Longevity & AgingSpatial Proteomics Maps Alzheimer's-Specific Microglial States in Human Brain
Using Multiplexed Ion Beam Imaging (MIBI) with up to 40 protein markers, researchers mapped nearly 94,000 microglia across five human brain regions. Rather than discrete subtypes, microglia fell along a continuous 'microglial state continuum' (MSC) tied to local brain microenvironments. In Alzheimer's disease brains, microglia skewed toward high-activation states marked by increased CD33 and CD44 and decreased HLA-DR, P2RY12, and ApoE—especially in hippocampal CA1. These findings were validated against single-nucleus chromatin accessibility data, linking proteomic states to epigenetic programs. The study establishes a quantitative spatial proteomic framework for understanding human microglial dysfunction in neurodegeneration.
