Animal models of Alzheimer's disease (AD) are typically maintained pathogen-free, missing the lifetime of peripheral infections that shape the aging human immune system. The role of brain-resident microglia as non-classical antigen-presenting cells (APCs) under this realistic inflammatory burden remains poorly defined. To address this gap, we subjected WT and APP/PS1 mice to sequential infections every two months from 2 to 8 months of age, with tissues harvested at 13 months. Using iterative bleaching extends multiplexity (IBEX) immunofluorescence, we profiled the resulting neuroimmune landscape across lymphoid, myeloid, glial, vascular, and amyloid compartments. Plaque-associated Iba1⁺ microglia upregulated the APC markers CD11c and MHC-II in both APP/PS1 mock and infected brains, indicating that amyloid pathology alone is sufficient to license the microglial APC program. STAT1 activation, in contrast, was conditional on infection: mock controls of both genotypes showed minimal STAT1 immunoreactivity, whereas APP/PS1-infected brains exhibited widespread parenchymal STAT1⁺ foci across the cortex and hippocampus -- a pattern absent from WT-infected brains, where STAT1⁺ signal remained restricted to periventricular regions. Iba1⁺ microglia were the dominant parenchymal source of STAT1⁺ signal, establishing them as the principal IFN responder in the infected AD brain. To test whether microglial STAT1 activation reflects local engagement with infiltrating T cells, we measured nearest-neighbor distances from each STAT1⁺Iba1⁺ microglia to CD8⁺ T cells and found that STAT1⁺ microglia were markedly closer to STAT1⁺CD8⁺ T cells than to STAT1^-CD8⁺ T cells -- a coupling most consistent with short-range paracrine IFN-γ signaling. Spatial mapping revealed that activated microglia, CD8⁺ and CD4⁺ T cells, reactive astrocytes, and vasculature converged into organized clusters surrounding Aβ⁺ plaques. Together, these data reframe microglia as anatomically defined APC partners for adaptive immunity in the infected AD parenchyma: amyloid plaques nucleate microglial APC licensing, while infiltrating CD8⁺ T cells deliver the IFN-γ signal that drives local STAT1 activation.