The impact of age, comorbidity, and current medication use on plasma p-tau217 in adolescents

Background: Adolescence is a critical period of neurodevelopment with the emergence of chronic medical conditions and increasing exposure to long-term medications. P-tau217 is a sensitive blood-based biomarker of neuropathology in older adults, yet its developmental behavior and susceptibility to common clinical factors in youth are unclear. Here we tested whether p-tau217 varies with age, comorbidity, or medication use during adolescence; and whether collection method (venous vs Tasso+ capillary) yields comparable concentrations. Methods: In an adolescent cohort, plasma p-tau217 was measured by Simoa HD-X. Paired venous and Tasso+ capillary samples were also analyzed from adult volunteers for methodological comparison. Results: In adolescents (n=41; mean age 16±2.6 years), p-tau217 did not correlate with age or BMI z-score and did not differ by psychiatric, cardiometabolic, or gastrointestinal comorbidity, nor by corresponding medication use. In contrast, p-tau217 concentrations were >10-fold higher in Tasso+ capillary plasma than venous plasma, a discordance replicated in paired adult samples. Conclusion: Plasma p-tau217 appears physiologically stable across common clinical variables in adolescence, but highly sensitive to biospecimen collection method. Venous and Tasso+ capillary plasma should not be directly compared or pooled until methodological differences are resolved. These data provide a developmental baseline and critical methodological caution for pediatric neuroscience and decentralized biomarker studies.