Psychoneuroimmunology (PNI) advancements may revolutionize personalized medicine by identifying systemic biomarkers that enhance diagnosis and treatment. Inflammatory pathwaysPathways connect personality traitsPersonalitypersonality traits with cognitive performance, aging-related disorders, and mortality risks. Studies have demonstrated the critical interactions between personality and various biological systems like the hypothalamic-pituitary-adrenal (HPA) axis. The gut-brain axis also affects behaviors and psychological states in older adults, with specific gut microbiota influencing cognition, mood, and personality. These findings underscore the practical implications of understanding personality-biology interactions. They can support preventive and personalized medicine for aging-associated disorders. Specifically, personality changes are prevalent in Alzheimer’s disease (AD) patients, impacting clinical management and caregiver stress. Non-cognitive factors, such as personality traitsPersonalitypersonality traits and psychiatric symptoms, may serve as early markers of AD. Traits like high Neuroticism and low Openness can predict initial AD stages, often before a formal diagnosis. Personality alterations in AD are also linked to cerebrospinal fluid (CSF) and vascular imaging biomarkers, which can track AD pathology and serve as predictors. Dynamic personality assessment can aid in timely diagnosis, monitoring progression, and evaluating treatments of AD. Understanding personality traitsPersonalitypersonality traits is crucial for predicting burnout, lifespan, and intervention success. Integrating personality and PNI biomarkers into patient profiles will support the development of personalized and systems medicine.