{"doi":"10.36837/chapman.000657","title":"Role of Hepatic Lipoprotein Receptor-related Protein 1 (LRP-1) on Amyloid Beta Pathology in a Mouse Model of Amyloidosis","abstract":"Title: Role of hepatic lipoprotein receptor related protein 1 on amyloid beta pathology in a mouse model of amyloidosis. Alzheimer’s disease (AD) is a chronic neurodegenerative disease caused by an abundance of extracellular neuritic plaques containing enormous amounts of amyloid beta (Aβ) and excessive numbers of tau-rich neurofibrillary tangles. AD is currently the seventh leading cause of death in the United States and is the most common cause for dementia in older adults, with limited disease-modifying treatments. Therefore, there is growing emphasis on elucidating mechanisms that can be targeted to prevent or delay the course of disease. In this regard, AD is considered a disease of the brain, and the contribution of the periphery in AD pathogenesis is understudied. The current study focuses on the crosstalk between the liver, the largest internal and metabolic organ, and the brain, the organ harboring the pathological hallmarks of AD. Specifically, we focus on the hepatic low-density lipoprotein receptor related protein-1 (LRP1) which is the major receptor involved in the peripheral clearance of Aβ. Our preliminary work on the same lines showed a reduction in hepatic LRP1 in alcohol-fed mice with a concomitant increase in brain Aβ. Therefore, we hypothesized that a decrease in hepatic LRP1 will reduce peripheral Aβ clearance and increase Aβ deposition in the brain to instigate or enhance AD pathology. For this, LRP1 was silenced specifically in the livers of APP/PS1 mice using LRP1 microRNA (miRNA) delivered by adeno-associated virus 8. (AAV8) and the hepato-specific thyroxine binding globulin (TBG) promoter, designated as AAV8.TBG.LRP1miRNA. Briefly, male APP/PS1 mice (four months at the time of injection) were divided into two groups, the AAV8 control group (n=6) and the AAV8 miRNA LRP1 group (n=7). 12 weeks after LRP1 silencing, behavioral studies including Y-maze, nesting behavior, and open-field testing, were performed, and mice were sacrificed. The brain, liver, and plasma were collected to measure Aβ load using immunoassays. After performing all these studies, we did see a difference between both the groups as hypothesized by observing the increase in brain Aβ, this further lead to see if this hypothesis did stand still in aged mice and how much role age plays in aggravating Aβ and Aβ plaque load. For this, the same mouse model of APP/PS1 male mice with hepato-specific LRP1 silencing but at 28 weeks were used and divided in two groups in the same way, the AAV8 control group (n=6) and the","journal":"Chapman University","year":2025,"id":565383,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"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":1222677,"name":"Urvashi Panchal","orcid":"0000-0002-3182-6150","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:56:28.709936Z","pmid":null,"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":[]}