Alzheimer's disease (AD) poses a growing global health challenge as populations age. Recent research highlights the crucial role of peripheral immunity in AD pathogenesis. This review explores how blood-brain barrier disruption allows peripheral immune cells to infiltrate the central nervous system (CNS), worsening neuroinflammation and disease progression. We examine recent findings on interactions between peripheral immune cells and CNS-resident microglia, forming a self-perpetuating inflammatory cycle leading to neuronal dysfunction. Moreover, this review emphasizes recent developments in the dysregulation of immune factors from both the periphery and CNS, and their impact on AD progression. With ongoing research and development of new therapeutic strategies, this review underscores the importance of modulating interactions between the peripheral immune system and CNS in AD therapy.