Blood-based biomarkers of agitation in Alzheimer's disease: Advances and future prospects

Agitation is a common neuropsychiatric symptom that becomes more prevalent as Alzheimer's disease (AD) increases in severity. The treatment of agitation is an urgent and unmet need due to the poor outcomes associated with it, its disruptive impact on patients and caregivers, and the lack of efficacious and safe treatments. Recent research on agitation in AD with blood-based biomarkers has advanced the search for its biomarkers beyond the brain and provides new insights to understand its mechanisms and improve treatments. Here, we reviewed studies of blood-based biomarkers of agitation in AD, which show that inflammatory biomarkers are increased in patients with agitation, may predict the development of agitation, and are associated with symptom severity. In addition, they may also track symptom severity and response to treatment. Other biomarkers associated with agitation include markers of oxidative stress, brain cholesterol metabolism, motor activity, and clusterin, a chaperone protein. These results are promising and need to be replicated. Preliminary evidence suggests a role for these biomarkers in interventional studies for agitation to predict and monitor treatment response, which may eventually help enrich study samples and deliver therapy likely to benefit individual patients. Advances in blood-based biomarkers of AD including those identified in "-omic" studies and high sensitivity assays provide opportunities to identify new biomarkers of agitation. Future studies of agitation and its treatment should investigate blood-based biomarkers to yield novel insights into the neurobiological mechanisms of agitation, monitoring symptoms and response to treatment, and to identify patients likely to respond to treatments.