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PaM are closely associated with amyloid-\u03b2 (A\u03b2) plaques, while CoM are enriched in the pyramidal layer of the CA2\/CA1 hippocampal subfields, where they frequently engulf neurons and associate with tau-positive tangles and phosphorylated \u03b1-synuclein. To elucidate the role of these microglial subtypes, we employed high-content neuropathology, integrating Deep Spatial Profiling (DSP), multiplex chromogenic immunohistochemistry and confocal microscopy, to comprehensively map and characterise their morphological and molecular signatures, as well as their neuropathological and astrocytic microenvironments, in AD and control post-mortem samples. PaM and PaM-associated astrocytes exhibited signatures related to complement system pathways, ErbB signalling, and metabolic and neurodegenerative processes. In contrast, CoM displayed markers associated with protein degradation and immune signalling pathways, including STING, TGF-\u03b2, and NF-\u03baB. While no direct association between CD8\u2009+\u2009T cells and either microglial type was observed, CD163\u2009+\u2009perivascular macrophages were frequently incorporated into PaM. 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