{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T17:17:18Z","timestamp":1763399838164,"version":"3.37.3"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS-PI113-01330"],"award-info":[{"award-number":["FIS-PI113-01330"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"crossref","award":["SAF2017-89613"],"award-info":[{"award-number":["SAF2017-89613"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002943","name":"Departament d'Innovaci\u00f3, Universitats i Empresa, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2014-PROD00032"],"award-info":[{"award-number":["2014-PROD00032"]}],"id":[{"id":"10.13039\/501100002943","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"FEDER","doi-asserted-by":"crossref","award":["FIS-PI113-01330; SAF2017-89613R; 2014-PROD00032"],"award-info":[{"award-number":["FIS-PI113-01330; SAF2017-89613R; 2014-PROD00032"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011104","name":"Universitat Aut\u00f2noma de Barcelona","doi-asserted-by":"publisher","award":["PIF grant"],"award-info":[{"award-number":["PIF grant"]}],"id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0217793","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T17:49:31Z","timestamp":1559324971000},"page":"e0217793","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetic parameters and mechanism of action of an efficient anti-A\u03b2 single chain antibody fragment"],"prefix":"10.1371","volume":"14","author":[{"given":"Gisela","family":"Esquerda-Canals","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquim","family":"Mart\u00ed-Cl\u00faa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8644-4304","authenticated-orcid":true,"given":"Sandra","family":"Villegas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,5,31]]},"reference":[{"key":"ref1","unstructured":"ALZFORUM | NETWORKING FOR A CURE n.d. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.alzforum.org\/\" xlink:type=\"simple\">http:\/\/www.alzforum.org\/<\/ext-link> (accessed February 10, 2015)."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1017\/erm.2016.11","article-title":"A\u03b2-Immunotherapeutic strategies: a wide range of approaches for Alzheimer\u2019s disease treatment","volume":"18","author":"L Montoliu-Gaya","year":"2016","journal-title":"Expert Rev Mol Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1192\/bjp.bp.115.167569","article-title":"Alzheimer\u2019s disease: The amyloid hypothesis on trial","volume":"208","author":"JR Harrison","year":"2016","journal-title":"Br J Psychiatry"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrd3505","article-title":"Strooper B De. The amyloid cascade hypothesis for Alzheimer\u2019s disease: an appraisal for the development of therapeutics","volume":"10","author":"E Karran","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2217\/imt.11.170","article-title":"Immunotherapy for Alzheimer\u2019s disease: from anti-\u03b2-amyloid to tau-based immunization strategies","volume":"4","author":"F Panza","year":"2012","journal-title":"Immunotherapy"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bcp.2013.12.020","article-title":"Immunotherapy for Alzheimer\u2019s disease","volume":"88","author":"T Wisniewski","year":"2014","journal-title":"Biochem Pharmacol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3389\/fnins.2014.00235","article-title":"New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimer\u2019s Disease","volume":"8","author":"JP Fuller","year":"2014","journal-title":"Front Neurosci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2217\/nmt-2016-0006","article-title":"A\u03b2 immunotherapy for Alzheimer\u2019s disease: where are we?","volume":"6","author":"J G\u00fcell-Bosch","year":"2016","journal-title":"Neurodegener Dis Manag"},{"key":"ref9","first-page":"3","article-title":"Prospective Therapies for Alzheimer Disease: Biomarkers, Clinical Trials and Preclinical Research","volume":"4","author":"J G\u00fcell-Bosch","year":"2016","journal-title":"Front. Clin. Drug Res.\u2014CNS Neurol. Disord"},{"key":"ref10","unstructured":"ClinicalTrials.gov. US Natl Institutes Heal Bethesda 1988. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">https:\/\/clinicaltrials.gov\/<\/ext-link> (accessed February 3, 2015)."},{"key":"ref11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1056\/NEJMoa1304839","article-title":"Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer\u2019s disease","volume":"370","author":"S Salloway","year":"2014","journal-title":"N Engl J Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1312889","article-title":"Phase 3 trials of solanezumab for mild-to-moderate Alzheimer\u2019s disease","volume":"370","author":"RS Doody","year":"2014","journal-title":"N Engl J Med"},{"key":"ref13","unstructured":"Biogen\/Eisai Halt Phase 3 Aducanumab Trials | ALZFORUM n.d. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.alzforum.org\/news\/research-news\/biogeneisai-halt-phase-3-aducanumab-trials\" xlink:type=\"simple\">https:\/\/www.alzforum.org\/news\/research-news\/biogeneisai-halt-phase-3-aducanumab-trials<\/ext-link> (accessed April 17, 2019)."},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/nbt1142","article-title":"Engineered antibody fragments and the rise of single domains","volume":"23","author":"P Holliger","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3390\/antib2020193","article-title":"In Vivo Applications of Single Chain Fv (Variable Domain) (scFv) Fragments","volume":"2","author":"P Monnier","year":"2013","journal-title":"Antibodies"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jalz.2011.05.2351","article-title":"Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer\u2019s Association Research Roundtable Workgroup","volume":"7","author":"RA Sperling","year":"2011","journal-title":"Alzheimers Dement"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"779","DOI":"10.2174\/1570159X01666160930121647","article-title":"Recombinant Antibody Fragments for Neurodegenerative Diseases.","volume":"15","author":"K Manoutcharian","year":"2017","journal-title":"Curr Neuropharmacol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"19109","DOI":"10.3390\/ijms140919109","article-title":"Single-Chain Fragment Variable Passive Immunotherapies for Neurodegenerative Diseases","volume":"14","author":"L Huang","year":"2013","journal-title":"Int J Mol Sci"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"11455","DOI":"10.1073\/pnas.97.21.11455","article-title":"Immunization against Alzheimer\u2019s beta-amyloid plaques via EFRH phage administration","volume":"97","author":"D Frenkel","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/bit.22576","article-title":"IgG-single chain Fv fusion protein therapeutic for alzheimer\u2019s disease: Expression in CHO cells and pharmacokinetics and brain delivery in the rhesus monkey","volume":"105","author":"RJ Boado","year":"2010","journal-title":"Biotechnol Bioeng"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"13120","DOI":"10.1021\/bi980712q","article-title":"Mutual Stabilization of V <sub>L<\/sub> and V <sub>H<\/sub> in Single-Chain Antibody Fragments, Investigated with Mutants Engineered for Stability <sup>\u2020<\/sup>","volume":"37","author":"A W\u00f6rn","year":"1998","journal-title":"Biochemistry"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1006\/jmbi.1999.2854","article-title":"Removal of the conserved disulfide bridges from the scFv fragment of an antibody: effects on folding kinetics and aggregation","volume":"290","author":"K Ramm","year":"1999","journal-title":"J Mol Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1006\/jmbi.2000.4265","article-title":"Stability engineering of antibody single-chain Fv fragments","volume":"305","author":"A W\u00f6rn","year":"2001","journal-title":"J Mol Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/BJ20101712","article-title":"An anti-A\u03b2 (amyloid \u03b2) single-chain variable fragment prevents amyloid fibril formation and cytotoxicity by withdrawing A\u03b2 oligomers from the amyloid pathway","volume":"437","author":"M Mar\u00edn-Argany","year":"2011","journal-title":"Biochem J"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/13506129.2017.1348347","article-title":"Towards the improvement in stability of an anti-A\u03b2 single-chain variable fragment, scFv-h3D6, as a way to enhance its therapeutic potential","volume":"24","author":"L Montoliu-Gaya","year":"2017","journal-title":"Amyloid"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"678","DOI":"10.4161\/mabs.25382","article-title":"Elongation of the C-terminal domain of an anti-amyloid \u03b2 single-chain variable fragment increases its thermodynamic stability and decreases its aggregation tendency","volume":"5","author":"G Rivera-Hern\u00e1ndez","year":"2013","journal-title":"MAbs"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"665","DOI":"10.4161\/mabs.25424","article-title":"Early intervention in the 3xTg-AD mice with an amyloid \u03b2-antibody fragment ameliorates first hallmarks of Alzheimer disease","volume":"5","author":"L Gim\u00e9nez-Llort","year":"2013","journal-title":"MAbs"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"660","DOI":"10.4161\/mabs.25428","article-title":"Loss of deep cerebellar nuclei neurons in the 3xTg-AD mice and protection by an anti-amyloid \u03b2 antibody fragment.","volume":"5","author":"G Esquerda-Canals","year":"2013","journal-title":"MAbs"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e0181480","DOI":"10.1371\/journal.pone.0181480","article-title":"Production of an anti-A\u03b2 antibody fragment in Pichia pastoris and in vitro and in vivo validation of its therapeutic effect","volume":"12","author":"L Montoliu-Gaya","year":"2017","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: intracellular A\u03b2 and synaptic dysfunction","volume":"39","author":"S Oddo","year":"2003","journal-title":"Neuron"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.neurobiolaging.2003.08.012","article-title":"Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer\u2019s disease","volume":"24","author":"S Oddo","year":"2003","journal-title":"Neurobiol Aging"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.neubiorev.2006.07.007","article-title":"Modeling behavioral and neuronal symptoms of Alzheimer\u2019s disease in mice: A role for intraneuronal amyloid","volume":"31","author":"L Gim\u00e9nez-Llort","year":"2007","journal-title":"Neurosci Biobehav Rev"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.brainres.2010.10.009","article-title":"Sex differences in \u03b2-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure","volume":"1366","author":"JC Carroll","year":"2010","journal-title":"Brain Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.bcp.2018.07.012","article-title":"Differential effects of apoE and apoJ mimetic peptides on the action of an anti-A\u03b2 scFv in 3xTg-AD mice","volume":"155","author":"L Montoliu-Gaya","year":"2018","journal-title":"Biochem Pharmacol"},{"article-title":"The Mouse Brain in Stereotaxic Coordinates","year":"2012","author":"KBJ Franklin","key":"ref35"},{"year":"2017","author":"J. G\u00fcell-Bosch","key":"ref36"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/1471-2202-9-81","article-title":"Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer\u2019s disease-related pathologies in male triple-transgenic mice","volume":"9","author":"MA Mastrangelo","year":"2008","journal-title":"BMC Neurosci"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3233\/JAD-170218","article-title":"An Intracellular Amyloid-\u03b2\/A\u03b2PP Epitope Correlates with Neurodegeneration in those Neuronal Populations Early Involved in Alzheimer\u2019s Disease.","volume":"59","author":"G Esquerda-Canals","year":"2017","journal-title":"J Alzheimer\u2019s Dis"},{"key":"ref39","first-page":"107","article-title":"Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features.","volume":"10","author":"M\u00c1 Garc\u00eda-Cabezas","year":"2016","journal-title":"Front Neuroanat"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0197-0186(96)00073-3","article-title":"Induction of tumor necrosis factor alpha in cultured glial cells by trimethyltin","volume":"30","author":"WE Maier","year":"1997","journal-title":"Neurochem Int"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/ncn3.20","article-title":"Disease-modifying therapy for Alzheimer\u2019s disease: Challenges and hopes","volume":"1","author":"A Iwata","year":"2013","journal-title":"Neurol Clin Neurosci"},{"key":"ref42","first-page":"45","article-title":"Pharmacokinetic parameters: which are necessary to define a drug substance?","volume":"134","author":"LZ Benet","year":"1984","journal-title":"Eur J Respir Dis Suppl"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1523\/JNEUROSCI.23-24-08532.2003","article-title":"Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-\/- knock-out mice","volume":"23","author":"P Das","year":"2003","journal-title":"J Neurosci"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3233\/JAD-2011-110230","article-title":"Anti-Amyloid-\u03b2 Single-Chain Antibody Brain Delivery Via AAV Reduces Amyloid Load But May Increase Cerebral Hemorrhages in an Alzheimer\u2019s Disease Mouse Model","volume":"27","author":"J Kou","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.neurobiolaging.2007.06.013","article-title":"Intramuscular delivery of a single chain antibody gene reduces brain Abeta burden in a mouse model of Alzheimer\u2019s disease","volume":"30","author":"Y-J Wang","year":"2009","journal-title":"Neurobiol Aging"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/22124","article-title":"Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse","volume":"400","author":"D Schenk","year":"1999","journal-title":"Nature"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"6144","DOI":"10.1523\/JNEUROSCI.1090-04.2004","article-title":"Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition","volume":"24","author":"DM Wilcock","year":"2004","journal-title":"J Neurosci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/78682","article-title":"Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease","volume":"6","author":"F Bard","year":"2000","journal-title":"Nat Med"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"8850","DOI":"10.1073\/pnas.151261398","article-title":"Peripheral anti-A antibody alters CNS and plasma A clearance and decreases brain A burden in a mouse model of Alzheimer\u2019s disease","volume":"98","author":"RB DeMattos","year":"2001","journal-title":"Proc Natl Acad Sci"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.abb.2012.02.022","article-title":"Engineered antibody approaches for Alzheimer\u2019s disease immunotherapy","volume":"526","author":"R Robert","year":"2012","journal-title":"Arch Biochem Biophys"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1093\/hmg\/ddv321","article-title":"Anti-A\u03b2 single-chain variable fragment antibodies exert synergistic neuroprotective activities in Drosophila models of Alzheimer\u2019s disease","volume":"24","author":"P Fernandez-Funez","year":"2015","journal-title":"Hum Mol Genet"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-014-1290-2","article-title":"Do current therapeutic anti-A\u03b2 antibodies for Alzheimer\u2019s disease engage the target?","volume":"127","author":"AD Watt","year":"2014","journal-title":"Acta Neuropathol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"773","DOI":"10.14348\/molcells.2015.0073","article-title":"Therapeutic Strategy for the Prevention of Pseudorabies Virus Infection in C57BL\/6 Mice by 3D8 scFv with Intrinsic Nuclease Activity","volume":"38","author":"G Lee","year":"2015","journal-title":"Mol Cells"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"548380","DOI":"10.4061\/2011\/548380","article-title":"Mechanisms of amyloid-Beta Peptide uptake by neurons: the role of lipid rafts and lipid raft-associated proteins","volume":"2011","author":"AY Lai","year":"2010","journal-title":"Int J Alzheimers Dis"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1615\/CritRevEukarGeneExpr.v20.i2.10","article-title":"Tumor necrosis factor-\u03b1 signaling in macrophages","volume":"20","author":"N Parameswaran","year":"2010","journal-title":"Crit Rev Eukaryot Gene Expr"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0217793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T23:50:15Z","timestamp":1721346615000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0217793"}},"subtitle":[],"editor":[{"given":"Stephen D.","family":"Ginsberg","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,5,31]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0217793","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2019,5,31]]}}}