Association of genetic risk score for Alzheimer's disease with late‐life body mass index in all of us: Evaluating reverse causation

• DOI: 10.1002/alz.14598
• Publication Date: 2025-04-07T04:29:32Z
• Authors: Minhyuk Choi; Scott C. Zimmerman; Peter T. Buto; Jingxuan Wang; Willa D. Brenowitz; Thomas J. Hoffmann; Adina Zeki Al Haz...; Katrina Kezios; M. Maria Glymour
• Keywords: Longitudinal Study

Abstract INTRODUCTION Decreases in body mass index (BMI) may be early consequences of Alzheimer's disease (AD) pathophysiological changes. Previous research the UK Biobank estimated that AD‐related genes began affecting BMI around age 47. We assessed whether this result could replicated using longitudinal data an independent cohort. METHODS Using All Us (AOU) ( N = 197,619, aged 30+) data, we linear mixed models for associations Z ‐scored AD‐Genetic Risk Score (AD‐GRS) with BMI, stratified by decade age. calculated earliest at which AD‐GRS was associated differences cross‐validated adjusted demographics. RESULTS Higher statistically lower participants 60–70 b −0.060 [−0.113, −0.007]). Best fitting suggested inverse association and emerged beginning ages 47–54. DISCUSSION AD accelerate age‐related weight loss starting middle Highlights Understanding when physiological changes from amyloid pathology begin is key prevention. Our findings indicate AD‐associated midlife loss, between 47 54 years. prevention should consider likely begins