Abstract
Peripheral immune cells play an important role in the pathology of Alzheimer's disease (AD), impacting processes such as amyloid and tau protein aggregation, glial activation, neuronal integrity, and cognitive decline. Here, we examine cutting-edge strategies - encompassing animal and cellular models - used to investigate the roles of peripheral immune cells in AD. Approaches such as antibody-mediated depletion, genetic ablation, and bone marrow chimeras in mouse models have been instrumental in uncovering T, B, and innate immune cell disease-modifying functions. However, challenges such as specificity, off-target effects, and differences between human and mouse immune systems underscore the need for more human-relevant models. Emerging multicellular models replicating critical aspects of human brain tissue and neuroimmune interactions increasingly offer fresh insights into the role of immune cells in AD pathogenesis. Refining these methodologies can deepen our understanding of immune cell contributions to AD and support the development of novel immune-related therapeutic interventions.