journal articles
A REVIEW OF EVIDENCE SUPPORTING AMYLOID BETA REDUCTION AS A SURROGATE ENDPOINT IN ALZHEIMER’S DISEASE
Tianle Chen, R. Matthew Hutchison, Carrie Rubel, Jennifer Murphy, Jing Xie, John O’Gorman, Gersham Dent, Geert Molenberghs, Maria Pia Sormani, Suzanne Hendrix, Oskar Hansson, Paul Aisen, Samantha Budd Haeberlein, Ying Tian
J Prev Alz Dis 2026;2(13)
Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disease driven by pathological depositions of proteins that accumulate over decades. Compelling genetic and neurobiological evidence suggests that amyloid accumulation in the brain initiates and drives early-stage AD. Measurement of fibrillar amyloid has been pivotal to the development and approval of disease-slowing treatments. Various biomarkers of AD pathophysiology provide evidence of target engagement and downstream effects on disease progression, and their use as surrogate endpoints may help identify and expeditiously bring new treatments to patients. In clinical trials, a surrogate endpoint serves as a substitute for a direct measurement of a patient’s clinical status, and its use can provide ethical, logistical, and economic advantages. Establishing biomarkers as surrogate endpoints involves evaluating scientific evidence through diverse statistical approaches to demonstrate their predictivity of clinical benefit. This article evaluated evidence supporting amyloid β plaque reduction as a surrogate endpoint in symptomatic AD by exploring regulatory considerations and guidelines for surrogate endpoints, examining the amyloid hypothesis and the current therapeutic landscape in AD, and presenting supporting evidence of surrogate endpoints from a recent clinical development program of AD.
CITATION:
Tianle Chen ; R. Matthew Hutchison ; Carrie Rubel ; Jennifer Murphy ; Jing Xie ; John O’Gorman ; Gersham Dent ; Geert Molenberghs ; Maria Pia Sormani ; Suzanne Hendrix ; Oskar Hansson ; Paul Aisen ; Samantha Budd Haeberlein ; Ying Tian (2025): A review of evidence supporting amyloid beta reduction as a surrogate endpoint in Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100458