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High-resolution imaging is used to test plaque penetrability and ECS diffusion properties. Two-photon shadow imaging identifies a dense cellular ring around plaques and altered diffusion through the amyloid core. Quantum dot and carbon nanotube tracking reveal heterogeneous diffusion parameters and phenotype-dependent nanoparticle density, with dysregulated extracellular matrix within plaques.",{"@graph":69,"@context":114},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nanoscopic-mapping-of-the-extracellular-space-in-amyloid-plaque-rich-cortex/439551/",{"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/nanoscopic-mapping-of-the-extracellular-space-in-amyloid-plaque-rich-cortex/439551.png","ImageObject",300,407,{"name":92,"@type":93},"Bintang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108],{"name":109,"@type":110,"acceptedAnswer":111},"What do the results suggest about the ECS around and inside plaques?","Question",{"text":112,"@type":113},"The ECS diffusion parameters are heterogeneous in and around plaques, with elevated diffusivity near and within plaques; the amyloid core also shows low nanoparticle density varying by plaque phenotype.","Answer","https://schema.org",{"og:url":83,"og:type":116,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":118,"canonical":83},"index,follow",{"doc_id":120,"site_id":62},439551,1790740448,{"code":4,"msg":5,"data":123},{"doc_id":120,"user_id":124,"nickname":92,"user_avatar":125,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":131,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":132,"faqs":133,"seo_title":134,"seo_description":67,"update_tm":135,"read_time":136},962085564381,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nNanoscopic Mapping of the Extracellular Space in Amyloid Plaque-rich Cortex  \nJuan Estaún-Panzano, Yulia Dembitskaya, Ivo Calaresu, Somen Nandi, Quentin Gresil, Evelyne Doudnikoff, Thierry Leste-Lasserre, Thierry Amédée, Laurent Cognet, Laurent Groc, Urs Valentin Nägerl,* and Erwan Bezard*  \nA hallmark of Alzheimer’s disease (AD) is the accumulation of amyloid plaques, primarily composed of misfolded amyloid 􀀂 (A􀀂) peptides. Complementary high-resolution imaging techniques are employed to investigate the plaque penetrability and the extracellular space (ECS) rheology in a mouse model ofAD. Two-photon shadow imaging in vivo confirms that a dense ring of cells surrounds cortical amyloid plaques but highlights the diffusional penetrability of the amyloid core. Quantum dot tracking unveils that ECS diffusional parameters are heterogeneous in and around plaques, with an elevated diffusivity within and around plaques compared to  \nwild-type-tissue. The amyloid core shows low nanoparticle density, varying by plaque phenotype. Carbon nanotube tracking confirms these altered local rheological properties at the level of the whole cortex of AD mice. Finally, the extracellular matrix is found to be dysregulated within the amyloid plaque, which may account for the observed alterations in diffusivity. This study provides fresh insights for understanding A􀀂 plaque penetration, a prerequisite for therapeutic development.  \nfunction, especially in the expanding aging population, becoming a significant socioeconomic burden for healthcare systems. [1] A recognized hallmark of the disease is the presence of amyloid plaques, primarily composed of misfolded amyloid 􀀂 (A􀀂) peptides, in the brain’s extracellular space (ECS) . [2,3]  \nAmong recent strategies to tackle the disease, amyloid plaque clearance and immune system modulation have raised hopes but still suffer from unsatisfactory outcomes. [4] As a consequence, the penetrability of brain tissue has come into focus as a potentially pivotal determinant oftherapeutic efficacy.[5] However, how different substances can navigate within the ECS remains poorly understood, let alone whether they can penetrate amyloid plaques. Deeper insights into the properties of the ECS are crucial, as it plays a key role in normal brain function[6] and disease progression. [7–9]  \n1. Introduction  \nAlzheimer’s disease (AD) poses significant challenges to researchers and clinicians due to its poorly understood etiology and pathophysiology. This condition profoundly affects cognitive  \nThis study presents an innovative experimental and analytical framework for dissecting the influence of the ECS rheology, i.e., a concept that encompasses diffusionability within the compartment and compartment dimensions, on molecular diffusionin the context of amyloid pathology. We used 2-photon shadow  \nJ. Estaún-Panzano, E. Doudnikoff, E. Bezard Institut des Maladies Neurodégénératives CNRS  \nUniversité de Bordeaux  \nUMR 5293, Bordeaux F-33000, France E-mail: [erwan.bezard@u-bordeaux.fr](erwan.bezard@u-bordeaux.fr)  \nY. Dembitskaya, I. Calaresu, T. Amédée, L. Groc, U. V. Nägerl Institut Interdisciplinaire de Neurosciences  \nCNRS  \nUniversité de Bordeaux  \nUMR 5297, Bordeaux F-33000, France E-mail: [valentin.nagerl@u-bordeaux.fr](valentin.nagerl@u-bordeaux.fr)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202515674](https://doi.org/10.1002/advs.202515674)[ ](https://doi.org/10.1002/advs.202515674)© 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.1002/advs.202515674  \nS. Nandi, Q. Gresil, L. Cognet Laboratoire Photonique Numérique et Nanosciences CNRS  \nUniversité de Bordeaux  \nUMR ","cbCaiqwDb9Yk2FRO","https://ap.wps.com/l/cbCaiqwDb9Yk2FRO","pdf",6913874,"English","# Introduction\n# Results\n## Shadow Imaging Reveals Amyloid Plaque Organization and Surrounding ECS Structure","[{\"question\":\"What do the results suggest about the ECS around and inside plaques?\",\"answer\":\"The ECS diffusion parameters are heterogeneous in and around plaques, with elevated diffusivity near and within plaques; the amyloid core also shows low nanoparticle density varying by plaque phenotype.\"}]","Nanoscopic Mapping of the Extracellular Space in Amyloid Plaque-rich Cortex | PDF",1790689187,48]