Approaches for studying neuroimmune interactions in Alzheimer’s disease

Emerging studies demonstrate the crucial role of peripheral immune cells in shaping Alzheimer’s disease (AD) pathology.Targeting peripheral immune cells presents promising therapeutic potential for AD treatment.In vivo and in vitro models are being used to study the specific role of peripheral immune cells in AD.Although research on neuroimmune interactions is in its early stages, we require a comprehensive understanding of how these interactions (involving peripheral immune cells) contribute to AD pathology. This can be achieved by integrating various cutting-edge approaches, including newer (e.g., humanized) animal models, human organoids, organ-on-chips, single-cell analyses, high-resolution imaging, and computational biology. Despite significant progress in understanding the roles of microglia (the brain’s resident immune cells) in Alzheimer’s disease (AD), much less is known about the contribution of peripheral immune cells to influencing AD pathology. Recent studies using rodent models and innovative human-based cellular systems are beginning to shed light on how peripheral immune cells infiltrate the brain and modulate disease progression. These promising cutting-edge approaches can expand our knowledge of the disease-modifying roles of these immune cells, paving the way for developing novel putative AD therapies. 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. Peripheral immune cells play an important role in the