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Microglial Responses to Alzheimer's Disease Pathology: Insights From "Omics" Studies
Aquene N Reid1,2, Suman Jayadev1,2,3, Katherine E Prater1
1Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.
Abstract:
Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes that are expressed in a microglia-specific manner. However, while alterations in microglial morphology and gene expression are observed in human postmortem brain tissue, the mechanisms by which microglia drive and contribute to AD pathology remain ill-defined. Numerous mouse models have been developed to facilitate the disambiguation of the biological mechanisms underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, the use of multiple technologies including bulk tissue and single cell transcriptomics, epigenomics, spatial transcriptomics, proteomics, lipidomics, and metabolomics have shed light on the heterogeneity of microglial phenotypes and molecular patterns altered in AD mouse models. Each of these 'omics technologies provide unique information and biological insight. Here, we review the literature on the approaches and findings of these methods and provide a synthesis of the knowledge generated by applying these technologies to mouse models of AD.
Insights
Microglia play a crucial role in Alzheimer's disease (AD) pathogenesis. This review synthesizes how various
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Human genetics implicates microglia in Alzheimer's disease (AD) pathogenesis.
- Microglial alterations are observed in human AD brains, but underlying mechanisms remain unclear.
- Mouse models are essential for dissecting AD's biological mechanisms.
Purpose of the Study:
- To review the application and findings of omics technologies in AD mouse models.
- To synthesize knowledge on microglial heterogeneity and molecular patterns in AD pathogenesis.
Main Methods:
- Review of literature utilizing transcriptomics (bulk, single-cell, spatial), epigenomics, proteomics, lipidomics, and metabolomics.
- Focus on studies employing various AD mouse models (amyloidosis, tauopathy, or both).
Main Results:
- Omics technologies reveal significant heterogeneity in microglial phenotypes within AD mouse models.
- These methods have identified altered molecular patterns associated with microglial dysfunction in AD.
- Each omics approach provides unique insights into microglial contributions to AD pathology.
Conclusions:
- Multi-omics approaches are critical for understanding the complex role of microglia in AD.
- Further research using these technologies in AD mouse models will elucidate microglial mechanisms driving disease.
- Synthesized knowledge from omics studies provides a foundation for developing targeted AD therapies.
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