Related Experiment Video
Updated: May 20, 2026
Biomarker Identification for Gender Specificity of Alzheimer's Disease Based on the Glial Transcriptome Profiles
Published on: May 20, 2024
Spatial proteomic analysis in human Alzheimer's disease brains enables identification of microenvironment-dependent
Paula Sanchez-Molina1,2, Dennis-Dominik Rosmus3,4,5, Dillon Brownell1,2
1Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA.
Abstract:
Disease-associated microglial states are thought to contribute to Alzheimer's disease (AD) progression, but characterizing them and their relationships to pathology remains challenging. Here we introduce CODEX-CNS-a multiplexed protein imaging technology with a custom data analysis pipeline for use in human brain samples. We profiled 704,706 cells in samples from the frontal cortex of 8 people with AD and 8 healthy controls and mapped features including blood-brain barrier, meningeal components and cell-cell interactions within the same tissue sections. Amongst the myeloid cell populations we identified, we found a border-associated macrophage-like microglial subset associated with aging. Further classifying myeloid cell subsets based on their spatial neighborhood, we identified a border-associated macrophage-like microglial subpopulation that was associated significantly with dense amyloid-β plaques, which we termed human plaque-associated microglia. This work offers insights into myeloid cell heterogeneity in AD and provides a new spatial approach to characterizing brain cells at the single-cell protein level.
Insights
Researchers identified a new type of microglia, human plaque-associated microglia, in Alzheimer's disease (AD) brains. This discovery offers novel spatial insights into brain cell heterogeneity and AD progression.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglial states are implicated in Alzheimer's disease (AD) progression.
- Characterizing these states and their link to AD pathology is challenging.
Purpose of the Study:
- To develop and apply a novel multiplexed protein imaging technology (CODEX-CNS) for high-resolution analysis of human brain samples.
- To characterize myeloid cell heterogeneity and spatial relationships within the context of Alzheimer's disease pathology.
Main Methods:
- Utilized CODEX-CNS technology to profile 704,706 cells in the frontal cortex of individuals with AD and healthy controls.
- Mapped cellular features, including blood-brain barrier components, meningeal elements, and cell-cell interactions within tissue sections.
- Employed a custom data analysis pipeline for spatial and cellular classification.
Main Results:
- Identified a border-associated macrophage-like microglial subset associated with aging.
- Discovered a distinct subpopulation, termed human plaque-associated microglia, significantly associated with dense amyloid-β plaques.
- Characterized myeloid cell heterogeneity and spatial organization in relation to AD pathology.
Conclusions:
- The study provides novel insights into myeloid cell heterogeneity in Alzheimer's disease.
- Introduces a powerful spatial approach for single-cell protein-level characterization of brain cells.
- Highlights the potential of human plaque-associated microglia as a key player in AD pathogenesis.
