ArticleActa neuropathologica communications2023
The localization of molecularly distinct microglia populations to Alzheimer's disease pathologies using QUIVER.
Article in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Pooled it
- Pancreatic hypersecretion of amyloid-forming human amylin dysregulates the neuro-immune axis and B cell development in a model of type-2 diabetes.Neurobiology of disease · 2025Article
- Assessing Co-Localization of ITM2B With Alzheimer's Disease and Limbic-Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Changes.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- Chromogen-based double immunohistochemical detection of mitochondrial respiratory chain deficiencies in human brain tissue.Acta neuropathologica communications · 2025Article
- A pathologic study of Perivascular pTDP-43 Lin bodies in LATE-NC.Acta neuropathologica communications · 2024Article
- The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing.Translational neurodegeneration · 2024Review
- A neuropathologic feature of brain aging: multi-lumen vascular profiles.Acta neuropathologica communications · 2023Article
- Quantitative multiplex immunohistochemistry with colorimetric staining (QUIVER) may still benefit from MILAN.Acta neuropathologica communications · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
New histological techniques are needed to examine protein distribution in human tissues, which can reveal cell shape and disease pathology connections. Spatial proteomics has changed the study of tumor microenvironments by identifying spatial relationships of immunomodulatory cells and proteins and contributing to the discovery of new cancer immunotherapy biomarkers. However, the fast-expanding toolkit of spatial proteomic approaches has yet to be systematically applied to investigate pathological alterations in the aging human brain in health and disease states. Moreover, post-mortem human brain tissue presents distinct technical problems due to fixation procedures and autofluorescence, which limit fluorescence methodologies. This study sought to develop a multiplex immunohistochemistry approach (visualizing the immunostain with brightfield microscopy). Quantitative multiplex Immunohistochemistry with Visual colorimetric staining to Enhance Regional protein localization (QUIVER) was developed to address these technical challenges. Using QUIVER, a ten-channel pseudo-fluorescent image was generated using chromogen removal and digital microscopy to identify unique molecular microglia phenotypes. Next, the study asked if the tissue environment, specifically the amyloid plaques and neurofibrillary tangles characteristic of Alzheimer's disease, has any bearing on microglia's cellular and molecular phenotypes. QUIVER allowed the visualization of five molecular microglia/macrophage phenotypes using digital pathology tools. The recognizable reactive and homeostatic microglia/macrophage phenotypes demonstrated spatial polarization towards and away from amyloid plaques, respectively. Yet, microglia morphology appearance did not always correspond to molecular phenotype. This research not only sheds light on the biology of microglia but also offers QUIVER, a new tool for examining pathological alterations in the brains of the elderly.
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