{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:22:26Z","timestamp":1790778146350,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Investissements d\u2019avenir","doi-asserted-by":"publisher","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Investissements d\u2019avenir","doi-asserted-by":"publisher","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u2018Institut Universitaire d\u2019Ing\u00e9nierie en Sant\u00e9\u2019 at Sorbonne University","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"\u2018Institut Universitaire d\u2019Ing\u00e9nierie en Sant\u00e9\u2019 at Sorbonne University","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]},{"name":"Laboratoire de Recherche en Technologies Chirurgicales Avanc\u00e9es","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"Laboratoire de Recherche en Technologies Chirurgicales Avanc\u00e9es","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]},{"name":"NeurATRIS","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"NeurATRIS","award":["ANR-11-INBS-0011-NeurATRIS"],"award-info":[{"award-number":["ANR-11-INBS-0011-NeurATRIS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia. No treatments have led to clinically meaningful impacts. A major obstacle for peripherally administered therapeutics targeting the central nervous system is related to the blood\u2013brain barrier (BBB). Ultrasounds associated with microbubbles have been shown to transiently and safely open the BBB. In AD mouse models, the sole BBB opening with no adjunct drugs may be sufficient to reduce lesions and mitigate cognitive decline. However, these therapeutic effects are for now mainly assessed in preclinical mouse models of amyloidosis and remain less documented in tau lesions. The aim of the present study was therefore to evaluate the effects of repeated BBB opening using low-intensity pulsed ultrasounds (LIPU) in tau transgenic P301S mice with two main readouts: tau-positive lesions and microglial cells. Our results show that LIPU-induced BBB opening does not decrease tau pathology and may even potentiate the accumulation of pathological tau in selected brain regions. In addition, LIPU-BBB opening in P301S mice strongly reduced microglia densities in brain parenchyma, suggesting an anti-inflammatory action. These results provide a baseline for future studies using LIPU-BBB opening, such as adjunct drug therapies, in animal models and in AD patients.<\/jats:p>","DOI":"10.3390\/ijms241512411","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T11:08:43Z","timestamp":1691060923000},"page":"12411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of Low-Intensity Pulsed Ultrasound-Induced Blood\u2013Brain Barrier Opening in P301S Mice Modeling Alzheimer\u2019s Disease Tauopathies"],"prefix":"10.3390","volume":"24","author":[{"given":"Amandine","family":"G\u00e9raudie","sequence":"first","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilien","family":"Riche","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"},{"name":"Department of Neurosurgery, Sorbonne University, APHP, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, GRC 23, Brain Machine Interface, APHP, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"},{"name":"Advanced Surgical Research Technology Lab, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4191-9114","authenticated-orcid":false,"given":"Tha\u00efs","family":"Lestra","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-9629","authenticated-orcid":false,"given":"Alexandre","family":"Trotier","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9o","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"},{"name":"Laboratoire Des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, Universit\u00e9 Paris-Saclay, CEA, CNRS, 18 Route du Panorama, 92265 Fontenay-Aux-Roses, France"},{"name":"Commissariat \u00e0 l\u2019Energie Atomique et aux \u00c9nergies Alternatives (CEA), Direction de la Recherche Fondamentale (DRF), Institut Fran\u00e7ois Jacob, MIRCen, 18 Route du Panorama, 92265 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9182-5846","authenticated-orcid":false,"given":"Bertrand","family":"Mathon","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"},{"name":"Department of Neurosurgery, Sorbonne University, APHP, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, GRC 23, Brain Machine Interface, APHP, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"},{"name":"Advanced Surgical Research Technology Lab, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Carpentier","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sorbonne University, APHP, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"},{"name":"Faculty of Medicine, Sorbonne University, GRC 23, Brain Machine Interface, APHP, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"},{"name":"Advanced Surgical Research Technology Lab, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9910-9932","authenticated-orcid":false,"given":"Beno\u00eet","family":"Delatour","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"ref_1","unstructured":"Prince, M., Wimo, A., Guerchet, M., Ali, G.C., Wu, Y.T., and Prina, M. (2015). World Alzheimer Report 2015, The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends, Alzheimer\u2019s Disease International."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s40265-023-01858-9","article-title":"Anti-Amyloid Monoclonal Antibodies Are Transformative Treatments That Redefine Alzheimer\u2019s Disease Therapeutics","volume":"83","author":"Cummings","year":"2023","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.neurol.2022.06.012","article-title":"High-Clearance Anti-Amyloid Immunotherapies in Alzheimer\u2019s Disease. Part 1: Meta-Analysis and Review of Efficacy and Safety Data, and Medico-Economical Aspects","volume":"178","author":"Villain","year":"2022","journal-title":"Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1001\/jamaneurol.2021.4161","article-title":"Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients with Early Alzheimer Disease","volume":"79","author":"Salloway","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/B978-0-323-85538-9.00008-0","article-title":"Finding the Falsification Threshold of the Toxic Proteinopathy Hypothesis in Neurodegeneration","volume":"192","author":"Espay","year":"2023","journal-title":"Handb. Clin. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer Disease Neuropathologic Changes with Cognitive Status: A Review of the Literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12385","DOI":"10.1002\/trc2.12385","article-title":"Alzheimer\u2019s Disease Drug Development Pipeline: 2023","volume":"9","author":"Cummings","year":"2023","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv. (TRCI)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1038\/s41591-023-02326-3","article-title":"Tau-Targeting Antisense Oligonucleotide MAPTRx in Mild Alzheimer\u2019s Disease: A Phase 1b, Randomized, Placebo-Controlled Trial","volume":"29","author":"Mummery","year":"2023","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1001\/jamaneurol.2022.1375","article-title":"Safety and Efficacy of Semorinemab in Individuals with Prodromal to Mild Alzheimer Disease","volume":"79","author":"Teng","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3233\/JAD-2011-110977","article-title":"Gantenerumab: A Novel Human Anti-A\u03b2 Antibody Demonstrates Sustained Cerebral Amyloid-\u03b2 Binding and Elicits Cell-Mediated Removal of Human Amyloid-\u03b2","volume":"28","author":"Bohrmann","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3389\/fnagi.2019.00373","article-title":"Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain","volume":"11","author":"Pardridge","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1148\/radiol.2202001804","article-title":"Noninvasive MR Imaging\u2013Guided Focal Opening of the Blood-Brain Barrier in Rabbits","volume":"220","author":"Hynynen","year":"2001","journal-title":"Radiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.ultrasmedbio.2004.04.010","article-title":"Cellular Mechanisms of the Blood-Brain Barrier Opening Induced by Ultrasound in Presence of Microbubbles","volume":"30","author":"Sheikov","year":"2004","journal-title":"Ultrasound Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.ultrasmedbio.2007.12.015","article-title":"Effect of Focused Ultrasound Applied with an Ultrasound Contrast Agent on the Tight Junctional Integrity of the Brain Microvascular Endothelium","volume":"34","author":"Sheikov","year":"2008","journal-title":"Ultrasound Med. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1158\/1078-0432.CCR-19-2182","article-title":"Ultrasound-Mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-Bound Versus Cremophor Formulations","volume":"26","author":"Zhang","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343re2","DOI":"10.1126\/scitranslmed.aaf6086","article-title":"Clinical Trial of Blood-Brain Barrier Disruption by Pulsed Ultrasound","volume":"8","author":"Carpentier","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1158\/1078-0432.CCR-18-3643","article-title":"Safety and Feasibility of Repeated and Transient Blood\u2013Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma","volume":"25","author":"Idbaih","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40035-021-00269-8","article-title":"Extensive Frontal Focused Ultrasound Mediated Blood\u2013Brain Barrier Opening for the Treatment of Alzheimer\u2019s Disease: A Proof-of-Concept Study","volume":"10","author":"Park","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3171\/2022.9.JNS221565","article-title":"Focused Ultrasound\u2013Mediated Blood-Brain Barrier Opening in Alzheimer\u2019s Disease: Long-Term Safety, Imaging, and Cognitive Outcomes","volume":"139","author":"Rezai","year":"2022","journal-title":"J. Neurosurg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13195-022-00981-1","article-title":"Pilot Study of Repeated Blood-Brain Barrier Disruption in Patients with Mild Alzheimer\u2019s Disease with an Implantable Ultrasound Device","volume":"14","author":"Epelbaum","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"32691","DOI":"10.1073\/pnas.1908658117","article-title":"Clinically Approved IVIg Delivered to the Hippocampus with Focused Ultrasound Promotes Neurogenesis in a Model of Alzheimer\u2019s Disease","volume":"117","author":"Dubey","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jord\u00e3o, J.F., Ayala-Grosso, C.A., Markham, K., Huang, Y., Chopra, R., McLaurin, J., Hynynen, K., and Aubert, I. (2010). Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-\u03b2 Plaque Load in the TgCRND8 Mouse Model of Alzheimer\u2019s Disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010549"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/brain\/awx052","article-title":"Combined Effects of Scanning Ultrasound and a Tau-Specific Single Chain Antibody in a Tau Transgenic Mouse Model","volume":"140","author":"Nisbet","year":"2017","journal-title":"Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13195-021-00809-4","article-title":"A Comparative Study of the Effects of Aducanumab and Scanning Ultrasound on Amyloid Plaques and Behavior in the APP23 Mouse Model of Alzheimer Disease","volume":"13","author":"Leinenga","year":"2021","journal-title":"Alz. Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.expneurol.2013.05.008","article-title":"Amyloid-\u03b2 Plaque Reduction, Endogenous Antibody Delivery and Glial Activation by Brain-Targeted, Transcranial Focused Ultrasound","volume":"248","author":"Scarcelli","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"278ra33","DOI":"10.1126\/scitranslmed.aaa2512","article-title":"Scanning Ultrasound Removes Amyloid-\u03b2 and Restores Memory in an Alzheimer\u2019s Disease Mouse Model","volume":"7","author":"Leinenga","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1148\/radiol.14140245","article-title":"Alzheimer Disease in a Mouse Model: MR Imaging-Guided Focused Ultrasound Targeted to the Hippocampus Opens the Blood-Brain Barrier and Improves Pathologic Abnormalities and Behavior","volume":"273","author":"Burgess","year":"2014","journal-title":"Radiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5396","DOI":"10.7150\/thno.28717","article-title":"Unilateral Focused Ultrasound-Induced Blood-Brain Barrier Opening Reduces Phosphorylated Tau from The RTg4510 Mouse Model","volume":"9","author":"Karakatsani","year":"2019","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jconrel.2022.07.026","article-title":"Ultrasound-Mediated Delivery of Novel Tau-Specific Monoclonal Antibody Enhances Brain Uptake but Not Therapeutic Efficacy","volume":"349","author":"Bajracharya","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.7150\/thno.34388","article-title":"Repeated Ultrasound Treatment of Tau Transgenic Mice Clears Neuronal Tau by Autophagy and Improves Behavioral Functions","volume":"9","author":"Pandit","year":"2019","journal-title":"Theranostics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.ultrasmedbio.2023.02.002","article-title":"Safety Profile of Low-Intensity Pulsed Ultrasound\u2013Induced Blood\u2013Brain Barrier Opening in Non-Epileptic Mice and in a Mouse Model of Mesial Temporal Lobe Epilepsy","volume":"49","author":"Mathon","year":"2023","journal-title":"Ultrasound Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ahmed, M.H., Hern\u00e1ndez-Verdin, I., Quissac, E., Lemaire, N., Guerin, C., Guyonnet, L., Zahr, N., Mouton, L., Santin, M., and Petiet, A. (2023). Low-Intensity Pulsed Ultrasound-Mediated Blood-Brain Barrier Opening Increases Anti-Programmed Death-Ligand 1 Delivery and Efficacy in Gl261 Mouse Model. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020455"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/j.ultrasmedbio.2010.06.005","article-title":"Multi-Modality Safety Assessment of Blood-Brain Barrier Opening Using Focused Ultrasound and Definity Microbubbles: A Short-Term Study","volume":"36","author":"Baseri","year":"2010","journal-title":"Ultrasound Med. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.14336\/AD.2021.0510","article-title":"The Applications of Focused Ultrasound (FUS) in Alzheimer\u2019s Disease Treatment: A Systematic Review on Both Animal and Human Studies","volume":"12","author":"Liu","year":"2021","journal-title":"Aging Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fnins.2018.00055","article-title":"Safety and Efficacy of Scanning Ultrasound Treatment of Aged APP23 Mice","volume":"12","author":"Leinenga","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1074\/jbc.M409876200","article-title":"Changed Conformation of Mutant Tau-P301L Underlies the Moribund Tauopathy, Absent in Progressive, Nonlethal Axonopathy of Tau-4R\/2N Transgenic Mice","volume":"280","author":"Terwel","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16144","DOI":"10.1038\/s41598-020-73151-8","article-title":"Improvement of Glymphatic-Lymphatic Drainage of Beta-Amyloid by Focused Ultrasound in Alzheimer\u2019s Disease Model","volume":"10","author":"Lee","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13024-017-0200-1","article-title":"Absence of CX3CR1 Impairs the Internalization of Tau by Microglia","volume":"12","author":"Perea","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of Microglia and Inhibition of Exosome Synthesis Halt Tau Propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/brain\/awv081","article-title":"Reactive Microglia Drive Tau Pathology and Contribute to the Spreading of Pathological Tau in the Brain","volume":"138","author":"Maphis","year":"2015","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ncb1901","article-title":"Transmission and Spreading of Tauopathy in Transgenic Mouse Brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ramirez, D.M.O., Whitesell, J.D., Bhagwat, N., Thomas, T.L., Ajay, A.D., Nawaby, A., Delatour, B., LaFaye, P., Knox, J.E., and Harris, J.A. (2023, June 22). Endogenous Pathology in Tauopathy Mice Progresses via Brain Networks|BioRxiv. Available online: https:\/\/www.biorxiv.org\/content\/10.1101\/2023.05.23.541792v1.","DOI":"10.1101\/2023.05.23.541792"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E4376","DOI":"10.1073\/pnas.1411649111","article-title":"Proteopathic Tau Seeding Predicts Tauopathy In Vivo","volume":"111","author":"Holmes","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12974-020-01749-w","article-title":"The Behavioural and Neuropathologic Sexual Dimorphism and Absence of MIP-3\u03b1 in Tau P301S Mouse Model of Alzheimer\u2019s Disease","volume":"17","author":"Sun","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open Source Software for Digital Pathology Image Analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/s41374-018-0057-0","article-title":"Principles and Approaches for Reproducible Scoring of Tissue Stains in Research","volume":"98","author":"Meyerholz","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41586-023-05788-0","article-title":"Microglia-Mediated T Cell Infiltration Drives Neurodegeneration in Tauopathy","volume":"615","author":"Chen","year":"2023","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12411\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:25:30Z","timestamp":1760127930000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,3]]},"references-count":48,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241512411"],"URL":"https:\/\/doi.org\/10.3390\/ijms241512411","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,3]]}}}