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Review
. 2025 Mar;73(3):519-538.
doi: 10.1002/glia.24666. Epub 2025 Jan 6.

Microglial Responses to Alzheimer's Disease Pathology: Insights From "Omics" Studies

Aquene N Reid  1   2 , Suman Jayadev  1   2   3 , Katherine E Prater  1
Affiliations
Review

Microglial Responses to Alzheimer's Disease Pathology: Insights From "Omics" Studies

Aquene N Reid et al. Glia. 2025 Mar.

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.

Keywords: Alzheimer's disease; lipidomics; metabolomics; microglia; mouse; transcriptomics.

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