[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-455255-105":59,"doc-detail-455255-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","natural-progression-of-meningeal-lymphatic-dysfunction-in-appps1-mice-creates-a-critical-window-for-alzheimers-disease-intervention","Natural progression of meningeal lymphatic dysfunction in APP/PS1 mice creates a critical window for Alzheimer's disease intervention","","Age-dependent links between meningeal lymphatic dysfunction and Alzheimer’s disease pathology are tested in APP/PS1 mice. Male APP/PS1 and wild-type controls are examined at 3, 6, and 9 months for cognition, meningeal lymphatic and deep cervical lymph node drainage, lymphatic structure/function, and Aβ pathology. Cognitive impairment emerges at 6–9 months, Aβ plaques appear at 6 months and progress by 9 months, and tracer drainage and LYVE-1 expression decline by 6 months. Findings support a critical early timeframe for intervention via lymphatic clearance mechanisms.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/natural-progression-of-meningeal-lymphatic-dysfunction-in-appps1-mice-creates-a-critical-window-for-alzheimers-disease-intervention/455255/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/natural-progression-of-meningeal-lymphatic-dysfunction-in-appps1-mice-creates-a-critical-window-for-alzheimers-disease-intervention/455255.png","ImageObject",300,407,{"name":92,"@type":93},"kopisore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the study’s main question about meningeal lymphatic dysfunction in AD models?","Question",{"text":113,"@type":114},"The study asks whether, without exogenous intervention, AD mouse models develop spontaneous meningeal lymphatic drainage dysfunction as Aβ pathology progresses.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"At what age do APP/PS1 mice show cognitive deficits and when do Aβ plaques appear?",{"text":118,"@type":114},"Significant cognitive deficits appear at 6 and 9 months, and Aβ plaques emerge at 6 months and progress by 9 months in APP/PS1 mice.",{"name":120,"@type":111,"acceptedAnswer":121},"How is meningeal lymphatic drainage assessed in the experiments?",{"text":122,"@type":114},"Meningeal lymphatic/deep cervical lymph node drainage is assessed by intracisternal injection of Texas Red dextran tracer, followed by evaluation of tracer penetration and lymphatic changes.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},455255,1790817210,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Volume 55 |Number 6  \n12-12-2025  \nNatural progression of meningeal lymphatic dysfunction in APP/PS1 mice creates a critical window for Alzheimer's diseaseintervention  \nZILONG SHENXIBIN ZHOUCHUNXIANG ZHOU  \nFollow this and additional works at:https://journals.tubitak.gov.tr/medical  \nPart of the Medical Sciences Commons  \nRecommended Citation  \nSHEN,Z,ZHOU,X,&ZHOU,C(2025).Natural progression of meningeal lymphatic dysfunction in APP/PS1 mice creates a critical window for Alzheimer's disease intervention.Turkish Journal of MedicalSciences 55(6):1576-1583.https://doi.org/10.55730/1300-0144.6116  \nThis work is licensed under a Creative Commons Attribution 4.0 International License.  \nThis Research Article is brought to you for free and open access by TÜBiTAK Academic Journals.It has beenaccepted for inclusion in Turkish Journal of Medical Sciences by an authorized editor of TÜBiTAK AcademicJournals.For more information,please contact academic.publications@tubitak.gov.tr  \n# Natural progression of meningeal lymphatic dysfunction in APP/PS1 mice creates acritical window for Alzheimer's disease intervention\n\nZilong SHEND,Xibin ZHOUD,Lin HED,Mingjie WUD,ChunxiangZHOU'D  \nDivision of Shanghan Lun,Department of Classical Chinese Medicine,Schoolof Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing,China  \n     Received:01.08.2025 ·  Accepted/Published Online:26.10.2025 ·  Final Version:12.12.2025       \nBackground/aim:Meningeal lymphatic vessels(mLVs)facilitate the clearance of toxic metabolites like amyloid-beta(Aβ)fromthe central nervous system.Dysfunction in MLVs is implicated in Alzheimers disease(AD).However,current knowledge relies onexogenous intervention models that fail to capture spontaneous mLV dedline during AD progression.In this study,we investigated theage-dependent corelation between mLV/deep cervical lymph node(dCLN)dysfunction and Aβ pathology in APP/PS1 mice under  \nMaterials and methods:APP/PSI and wild-type(WT)mice at 3,6,and9 months of age were evaluated.Cognitive function was testedusing the Morris water maze.mLV/dCLN drainage was assessed by intracisternal Texas Red dextran 3 injection.Lymphatic structure/function and Aβpathology were analyzed via immunohistochemistry,immunofluorescence,and tracer penetration.  \nResults:APP/PS1 mice developed significant cognitive deficits at 6 and 9 months.Aβ plaques emerged at 6months and progressedby 9 months in APP/PS1 mice,but were absent in controls.At6months,APP/PS1mice had reduced tracer drainage in mLVs/dCLNs,decreased LYVE-1 expression,and impaired tracer penetration in the hippocampus/cortex compared to WT mice.  \nConclusion:Lymphatic functionaldedline starts at 6-months old,providinga critical timeframe for earlyADintervention.Our findingsunderscore the value of the APP/PS1 model for studying lymphatic clearance mechanisms in AD.  \nKey words:Meningeallymphatic vessels,deep cervicallymph nodes,APP/PS1 mice,Alzheimer's disease,Aβ  \n## 1.Introduction\n\nbe an important period for the accelerated deterioration ofAβ pathology.However,existing studies of mLVs damagein AD models rely exclusively on exogenous interventionmethods such as photodynamic ablation [9-11].Althoughthese studies have confirmed that mLVs ablation canaggravate Aβ deposition and induce oligodendrocyteabnormalities [9]and aggravate neurological damageafter viral infection [10],it is difficult to truly reflect theprogressive functional decline of mLVs in the naturalcourse of AD in such artificial intervention models.  \nIn 2015,Louveau et al.[1]made a breakthrough inconfirming the key role of human meningeal lymphaticvessels(mLVs)inthe drainage ofthecentralnervoussystem.This discovery challenged traditional understandings andshowed that the glymphatic system and mLVs in the brainare the primary pathway for clearing toxic metabolitessuch as amyloid-beta(Aβ)[2].mLV dysfunction leadsto abnormal Aβ deposition and is closely related to theneurodegenerative pathology of Alzheimer's disease(AD)[3].This","cbCaig0diDlQ79Tc","https://ap.wps.com/l/cbCaig0diDlQ79Tc","pdf",842918,"English","# Natural progression of meningeal lymphatic dysfunction in APP/PS1 mice creates a critical window for Alzheimer's disease intervention\n## 1. Introduction\n## 2. Materials and methods","[{\"question\":\"What is the study’s main question about meningeal lymphatic dysfunction in AD models?\",\"answer\":\"The study asks whether, without exogenous intervention, AD mouse models develop spontaneous meningeal lymphatic drainage dysfunction as Aβ pathology progresses.\"},{\"question\":\"At what age do APP/PS1 mice show cognitive deficits and when do Aβ plaques appear?\",\"answer\":\"Significant cognitive deficits appear at 6 and 9 months, and Aβ plaques emerge at 6 months and progress by 9 months in APP/PS1 mice.\"},{\"question\":\"How is meningeal lymphatic drainage assessed in the experiments?\",\"answer\":\"Meningeal lymphatic/deep cervical lymph node drainage is assessed by intracisternal injection of Texas Red dextran tracer, followed by evaluation of tracer penetration and lymphatic changes.\"}]","Natural progression of meningeal lymphatic dysfunction in APP/PS1 mice creates a critical window for Alzheimer's disease intervention | PDF",1790742482,23]