Abstract
Alzheimers Dement. 2026 Sep;22(9):e71829. doi: 10.1002/alz.71829.
ABSTRACT
The therapeutic landscape of Alzheimer's disease (AD) is rapidly evolving with the clinical adoption of anti-amyloid monoclonal antibodies (mAbs) despite an incomplete understanding of disease mechanisms, progression, and heterogeneity. Designing both observational longitudinal cohorts and clinical trials with novel mAbs in mind is imperative. These studies should capture mAb type, dosing, duration, degree of amyloid clearance, and downstream effects on neurodegeneration to interpret outcomes. Observational cohorts can compare treated and untreated populations, track biomarker trajectories, assess co-pathologies, and evaluate social determinants of health. Future trials must address variability in treatment response, identify resistant subgroups, and include long-term follow-up to assess durability and post-treatment effects. Combination therapy trials should be stage specific, pairing novel agents with mAbs and incorporating broader stratification beyond traditional biomarkers to reflect clinical and pathological heterogeneity. Integrating biological and clinical outcomes, with digital biomarkers and responder-enrichment strategies will enable more precise, mechanism-driven, and individualized therapeutic approaches in AD.
PMID:42750195 | DOI:10.1002/alz.71829