BackgroundV-set and immunoglobulin domain containing 4 (VSIG4) emerges as a significant player in the immune system pathways. It has been previously identified as a potential hub gene for Alzheimer's disease (AD) and aging, underscoring its importance in understanding these conditions.ObjectiveThis study aimed to evaluate the diagnostic potential of serum VSIG4 and identify trends in serum VSIG4 in relationship with other biomarkers and neurological tests.MethodsELISA was used to measure the serum concentration of VSIG4 in AD, compared to healthy subjects. The relationship between VSIG4 levels and the age of the subjects, as well as other AD-related serum proteins and various measures of cognition was examined.ResultsVSIG4 was significantly elevated in the serum of AD patients compared to healthy controls (p = 0.0074). Significant correlations were identified between serum VSIG4 and other notable proteins related to AD and inflammation, such as total tau, neurofilament light (NfL), YKL-40, CD14, FABP3, and TNF-α. Significant correlations were also identified between VSIG4 concentration and the results of neurological tests.ConclusionsSerum VSIG4 may reflect neuroinflammation and altered lipid processing, affecting the cognitive performance of AD and aging.