β2-Microglobulin and the ageing brain

β2-microglobulin (β2M) has long been treated as a generic marker of immune activation, kidney function, or cancer prognosis. However, emerging mechanistic evidence suggests that β2M may actively contribute to brain ageing by influencing neurogenesis, synaptic function, and cognitive performance. This study conducted a knowledge-mapping analysis, showing that β2M research is highly fragmented across themes including haematologic malignancy prognosis, systemic inflammation and cytokine networks, cerebrospinal fluid biomarkers, and neurodegeneration. By integrating keyword clustering, co-occurrence structure, and burst detection, the analysis supports reframing β2M as a cross-context biomarker candidate for the ageing brain and outlines a research roadmap. The key next step is to determine whether β2M acts as a causal driver, a circulating ageing signal, or a context-dependent modifier across brain-ageing contexts. Priorities include harmonised measurement and reporting, stronger multi-compartment evidence linking peripheral and central β2M, longitudinal brain-ageing endpoints, and study designs that incorporate modifiable lifestyle-related risk architecture to improve comparability and translational value in immune-brain ageing research.