{"doi":"10.1002/alz.12312","title":"Systematic in silico analysis of clinically tested drugs for reducing amyloid‐beta plaque accumulation in Alzheimer's disease","abstract":"INTRODUCTION: Despite strong evidence linking amyloid beta (Aβ) to Alzheimer's disease, most clinical trials have shown no clinical efficacy for reasons that remain unclear. To understand why, we developed a quantitative systems pharmacology (QSP) model for seven therapeutics: aducanumab, crenezumab, solanezumab, bapineuzumab, elenbecestat, verubecestat, and semagacestat. METHODS: Ordinary differential equations were used to model the production, transport, and aggregation of Aβ; pharmacology of the drugs; and their impact on plaque. RESULTS: The calibrated model predicts that endogenous plaque turnover is slow, with an estimated half-life of 2.75 years. This is likely why beta-secretase inhibitors have a smaller effect on plaque reduction. Of the mechanisms tested, the model predicts binding to plaque and inducing antibody-dependent cellular phagocytosis is the best approach for plaque reduction. DISCUSSION: A QSP model can provide novel insights to clinical results. Our model explains the results of clinical trials and provides guidance for future therapeutic development.","journal":"Alzheimer s & Dementia","year":2021,"id":163327,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.782,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":682973,"name":"Raibatak Das","orcid":null,"position":1,"is_corresponding":false},{"id":682974,"name":"Hafiz Mohmmad‐Abdul","orcid":null,"position":2,"is_corresponding":false},{"id":329002,"name":"Lin Lin","orcid":"0000-0001-6402-2995","position":3,"is_corresponding":false},{"id":19610,"name":"Bradley T. Hyman","orcid":"0000-0002-7959-9401","position":4,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":5,"is_corresponding":false},{"id":231554,"name":"Mark W. Albers","orcid":"0000-0001-7855-3455","position":6,"is_corresponding":false},{"id":230262,"name":"Robert A. Rissman","orcid":"0000-0001-9245-8278","position":7,"is_corresponding":false},{"id":476629,"name":"John M. Burke","orcid":"0000-0002-5144-6710","position":8,"is_corresponding":false},{"id":682359,"name":"Joshua F. Apgar","orcid":"0000-0002-3396-1874","position":9,"is_corresponding":false},{"id":682975,"name":"Lucia Wille","orcid":null,"position":10,"is_corresponding":false},{"id":682360,"name":"Lore Gruenbaum","orcid":"0000-0002-7928-5496","position":11,"is_corresponding":false},{"id":682361,"name":"Fei Hua","orcid":"0000-0001-7728-2155","position":12,"is_corresponding":false},{"id":682358,"name":"Kumpal Madrasi","orcid":"0000-0002-1442-8919","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:45:17.971865Z","pmid":"33938131","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":[]}