{"doi":"10.1002/alz.14598","title":"Association of genetic risk score for Alzheimer's disease with late‐life body mass index in all of us: Evaluating reverse causation","abstract":"INTRODUCTION: Decreases in body mass index (BMI) may be early consequences of Alzheimer's disease (AD) pathophysiological changes. Previous research in the UK Biobank estimated that AD-related genes began affecting BMI around age 47. We assessed whether this result could be replicated using longitudinal data in an independent cohort. METHODS: Using All of Us (AOU) (N = 197,619, aged 30+) data, we estimated linear mixed models for associations of Z-scored AD-Genetic Risk Score (AD-GRS) with BMI, stratified by decade of age. We calculated the earliest age at which AD-GRS was associated with differences in BMI using cross-validated models adjusted for demographics. RESULTS: Higher AD-GRS was statistically associated with lower BMI in participants aged 60-70 (b = -0.060 [-0.113, -0.007]). Best fitting models suggested the inverse association of AD-GRS and BMI emerged beginning at ages 47-54. DISCUSSION: AD genes accelerate age-related weight loss starting in middle age. HIGHLIGHTS: Understanding when physiological changes from amyloid pathology begin is key for AD prevention. Our findings indicate that AD-associated genes accelerate midlife weight loss, starting between 47 and 54 years. AD prevention research should consider that disease pathology likely begins by middle age.","journal":"Alzheimer s & Dementia","year":2025,"id":523042,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5225,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":486557,"name":"Scott C. Zimmerman","orcid":"0000-0002-4431-6520","position":1,"is_corresponding":false},{"id":1133247,"name":"Peter Buto","orcid":"0000-0001-5052-6009","position":2,"is_corresponding":false},{"id":1395091,"name":"Jingxuan Wang","orcid":"0000-0002-1570-7266","position":3,"is_corresponding":false},{"id":293445,"name":"Willa D. Brenowitz","orcid":null,"position":4,"is_corresponding":false},{"id":1219657,"name":"Thomas J. Hoffmann","orcid":"0000-0003-4129-9478","position":5,"is_corresponding":false},{"id":305268,"name":"Adina Zeki Al Hazzouri","orcid":"0000-0002-6006-321X","position":6,"is_corresponding":false},{"id":740897,"name":"Katrina Kezios","orcid":"0000-0001-7115-032X","position":7,"is_corresponding":false},{"id":106142,"name":"M. Maria Glymour","orcid":"0000-0001-9644-3081","position":8,"is_corresponding":false},{"id":1031103,"name":"Minhyuk Choi","orcid":"0009-0000-6658-5054","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:49:58.707747Z","pmid":"40189781","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}