Predicting symptom onset and clinical progression with blood biomarkers of Alzheimer disease - PROJECT SUMMARY This Mentored Quantitative Research Career Development Award consists of an integrated career development plan and research project designed to enable Dr. Kellen Petersen to become an independent investigator focused on applying advanced mathematical and computational models to the study of Alzheimer Disease (AD) and blood-based biomarkers. Washington University School of Medicine is a global leader in medical research and an important center of AD research with many recognized leaders in the field. Dr. Petersen will greatly benefit from such an active research environment with its many resources and support structure. Dr. Petersen’s career development plan consists of a detailed training program and assembles an interdisciplinary team of highly regarded researchers to support his growth in the key areas of AD fluid and neuroimaging biomarkers, cognitive aging, advanced statistical methods, and clinical trial design. The proposed project will integrate five high performing, complementary plasma biomarkers of Aβ42/Aβ40, %p-tau217, NfL, GFAP, and eMTBR-tau243 with demographic, genetic, and comorbidity data to rigorously develop validated diagnostic and prognostic models. Leveraging rich phenotyping in the Knight ADRC for model construction and external cohorts (ADNI, A4, and AHEAD 3-45) for replication, Dr. Petersen will apply machine-learning classifiers, latent “biomarker clock” modeling, and joint modeling techniques to predict (1) two-year cognitive decline, (2) symptomatic AD onset, and (3) loss of functional independence. Systematic comparisons of single-visit versus longitudinal blood draws, detailed analytical workflows, and pre-specified performance benchmarks will yield robust models that will streamline trial enrichment and deliver actionable prognostic tools to clinicians, patients, and caregivers. Concurrent coursework and training in survival and joint modeling, immersive biomarker and clinical trial workshops, leadership development, manuscript writing training, and guided mentorship will ensure his growth, development, and mastery of domain knowledge and a clear trajectory to independent R-level funding. Ultimately, this work combining cutting-edge modeling with scalable blood-based biomarker tests will shorten clinical trial timelines, enable earlier and more informed therapeutic decisions, and empower the more than seven million Americans living with or at risk for Alzheimer disease with personalized prognostic information as blood-based biomarkers enter routine practice.
