{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:06:06Z","timestamp":1791266766113,"version":"4.1.0"},"reference-count":132,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T00:00:00Z","timestamp":1467244800000},"content-version":"unspecified","delay-in-days":181,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Expert Rev. Mol. Med."],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Current therapies to treat Alzheimer's disease (AD) are focused on ameliorating symptoms instead of treating the underlying causes of AD. The accumulation of amyloid<jats:italic>\u03b2<\/jats:italic>(A<jats:italic>\u03b2<\/jats:italic>) oligomers, whether by an increase in production or by a decrease in clearance, has been described as the seed that initiates the pathological cascade in AD. Developing therapies to target these species is a vital step in improving AD treatment. A<jats:italic>\u03b2<\/jats:italic>-immunotherapy, especially passive immunotherapy, is a promising approach to reduce the A<jats:italic>\u03b2<\/jats:italic>burden. Up to now, several monoclonal antibodies (mAbs) have been tested in clinical trials on humans, but none of them have passed Phase III. In all likelihood, these trials failed mainly because patients with mild-to-moderate AD were recruited, and thus treatment may have been too late to be effective. Therefore, many ongoing clinical trials are being conducted in patients at the prodromal stage. New structures based on antibody fragments have been engineered intending to improve efficacy and safety. This review presents the properties of this variety of developing treatments and provides a perspective on state-of-the-art of passive A<jats:italic>\u03b2<\/jats:italic>-immunotherapy in AD.<\/jats:p>","DOI":"10.1017\/erm.2016.11","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T10:09:02Z","timestamp":1467281342000},"source":"Crossref","is-referenced-by-count":36,"title":["A<i>\u03b2<\/i>-Immunotherapeutic strategies: a wide range of approaches for Alzheimer's disease treatment"],"prefix":"10.1017","volume":"18","author":[{"given":"Laia","family":"Montoliu-Gaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Villegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2016,6,30]]},"reference":[{"key":"S1462399416000119_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"S1462399416000119_ref111","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.10.039"},{"key":"S1462399416000119_ref83","doi-asserted-by":"publisher","DOI":"10.1021\/bi049933o"},{"key":"S1462399416000119_ref107","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91553-D"},{"key":"S1462399416000119_ref19","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1016\/S0021-9258(18)53650-4","article-title":"Beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms","volume":"268","author":"Haass","year":"1993","journal-title":"Journal of Biological Chemistry"},{"key":"S1462399416000119_ref68","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2009.10.005"},{"key":"S1462399416000119_ref49","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2011.578573"},{"key":"S1462399416000119_ref57","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt246"},{"key":"S1462399416000119_ref16","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3505"},{"key":"S1462399416000119_ref99","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.2210"},{"key":"S1462399416000119_ref27","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(02)00029-3"},{"key":"S1462399416000119_ref128","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2013.05.027"},{"key":"S1462399416000119_ref64","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.03.011"},{"key":"S1462399416000119_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.045"},{"key":"S1462399416000119_ref77","doi-asserted-by":"publisher","DOI":"10.1038\/nm890"},{"key":"S1462399416000119_ref112","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63360-3"},{"key":"S1462399416000119_ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3028"},{"key":"S1462399416000119_ref17","doi-asserted-by":"publisher","DOI":"10.1038\/19077"},{"key":"S1462399416000119_ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.11.047"},{"key":"S1462399416000119_ref92","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2008.03.004"},{"key":"S1462399416000119_ref51","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":"Journal of Alzheimer's Diseases"},{"key":"S1462399416000119_ref7","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"S1462399416000119_ref126","doi-asserted-by":"publisher","DOI":"10.4155\/tde.13.21"},{"key":"S1462399416000119_ref105","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2005.04.020"},{"key":"S1462399416000119_ref127","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0187-4"},{"key":"S1462399416000119_ref37","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nrneurol.2012.128","article-title":"Alzheimer disease: amyloid-\u03b2 immunotherapy CAD106 passes first safety test in patients with Alzheimer disease","volume":"8","author":"Kingwell","year":"2012","journal-title":"Nature Reviews Neurology"},{"key":"S1462399416000119_ref76","first-page":"672","article-title":"The role of RAGE in amyloid-\u03b2 peptide-mediated pathology in Alzheimer's disease","volume":"10","author":"Schmidt","year":"2009","journal-title":"Current Opinion on Investigational Drugs"},{"key":"S1462399416000119_ref121","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24795"},{"key":"S1462399416000119_ref93","doi-asserted-by":"publisher","DOI":"10.2174\/156720510791050876"},{"key":"S1462399416000119_ref18","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-23226-5_5"},{"key":"S1462399416000119_ref98","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)01790-X"},{"key":"S1462399416000119_ref100","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.564013"},{"key":"S1462399416000119_ref56","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3233\/JAD-140741","article-title":"The murine version of BAN2401 (mAb158) selectively reduces amyloid-\u03b2 protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice","volume":"43","author":"Tucker","year":"2015","journal-title":"Journal of Alzheimer's Disease"},{"key":"S1462399416000119_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.040"},{"key":"S1462399416000119_ref122","doi-asserted-by":"publisher","DOI":"10.1007\/s004180050266"},{"key":"S1462399416000119_ref34","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-009-0070-5"},{"key":"S1462399416000119_ref90","doi-asserted-by":"publisher","DOI":"10.1021\/bi035038d"},{"key":"S1462399416000119_ref80","doi-asserted-by":"publisher","DOI":"10.1038\/nm1635"},{"key":"S1462399416000119_ref73","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1994.tb00854.x"},{"key":"S1462399416000119_ref130","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002230"},{"key":"S1462399416000119_ref52","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.1538"},{"key":"S1462399416000119_ref35","unstructured":"Schneeberger A. (2015) 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders, Nice, France"},{"key":"S1462399416000119_ref132","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.174"},{"key":"S1462399416000119_ref118","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1523\/JNEUROSCI.23-24-08532.2003","article-title":"Amyloid-\u03b2 immunization effectively reduces amyloid deposition in FcR gamma-\/- knock-out mice","volume":"23","author":"Das","year":"2003","journal-title":"Journal of Neuroscience"},{"key":"S1462399416000119_ref72","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2010.01088.x"},{"key":"S1462399416000119_ref123","doi-asserted-by":"publisher","DOI":"10.1038\/312162a0"},{"key":"S1462399416000119_ref131","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057606"},{"key":"S1462399416000119_ref43","doi-asserted-by":"publisher","DOI":"10.1038\/78682"},{"key":"S1462399416000119_ref75","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5571"},{"key":"S1462399416000119_ref69","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2009.22.6.1395256"},{"key":"S1462399416000119_ref94","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.25424"},{"key":"S1462399416000119_ref120","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.06.013"},{"key":"S1462399416000119_ref46","unstructured":"Black R. (2009) Immunotherapy regimes dependent on ApoE status (US Patent) US 20090155256 A1"},{"key":"S1462399416000119_ref91","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806766200"},{"key":"S1462399416000119_ref2","unstructured":"Alzheimer's Disease International. (2013) World Alzheimer Report 2013: Journey of Caring."},{"key":"S1462399416000119_ref22","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-4257(98)80035-1"},{"key":"S1462399416000119_ref45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2351"},{"key":"S1462399416000119_ref101","doi-asserted-by":"publisher","DOI":"10.1038\/nbt962"},{"key":"S1462399416000119_ref59","unstructured":"Sevigny J. (2015) 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders, Nice, France"},{"key":"S1462399416000119_ref86","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzn052"},{"key":"S1462399416000119_ref89","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200410047"},{"key":"S1462399416000119_ref114","doi-asserted-by":"publisher","DOI":"10.1038\/22124"},{"key":"S1462399416000119_ref74","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.01.014"},{"key":"S1462399416000119_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2008.03.007"},{"key":"S1462399416000119_ref103","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2008.04.013"},{"key":"S1462399416000119_ref15","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2009.99"},{"key":"S1462399416000119_ref47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151261398"},{"key":"S1462399416000119_ref82","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.02.022"},{"key":"S1462399416000119_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"S1462399416000119_ref20","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2168"},{"key":"S1462399416000119_ref61","doi-asserted-by":"publisher","DOI":"10.1038\/nature.2015.18031"},{"key":"S1462399416000119_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"S1462399416000119_ref85","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.09.008"},{"key":"S1462399416000119_ref24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03578.x"},{"key":"S1462399416000119_ref31","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt246"},{"key":"S1462399416000119_ref23","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.17.1.17"},{"key":"S1462399416000119_ref28","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00114"},{"key":"S1462399416000119_ref78","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10498"},{"key":"S1462399416000119_ref1","unstructured":"Alzheimer's Disease International. (2014) World Alzheimer Report 2014: Dementia and Risk Reduction"},{"key":"S1462399416000119_ref87","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703793104"},{"key":"S1462399416000119_ref10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1197623"},{"key":"S1462399416000119_ref21","doi-asserted-by":"publisher","DOI":"10.1021\/bi00069a001"},{"key":"S1462399416000119_ref25","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7085"},{"key":"S1462399416000119_ref62","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-70"},{"key":"S1462399416000119_ref39","doi-asserted-by":"publisher","DOI":"10.2174\/1567205012666150302154121"},{"key":"S1462399416000119_ref53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4742-11.2012"},{"key":"S1462399416000119_ref71","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-90"},{"key":"S1462399416000119_ref38","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12168"},{"key":"S1462399416000119_ref44","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304839"},{"key":"S1462399416000119_ref60","doi-asserted-by":"publisher","DOI":"10.1126\/science.349.6247.464"},{"key":"S1462399416000119_ref6","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0100-y"},{"key":"S1462399416000119_ref11","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2620"},{"key":"S1462399416000119_ref40","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-100195"},{"key":"S1462399416000119_ref41","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1142"},{"key":"S1462399416000119_ref32","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000159740.16984.3C"},{"key":"S1462399416000119_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.04.011"},{"key":"S1462399416000119_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70140-0"},{"key":"S1462399416000119_ref42","doi-asserted-by":"publisher","DOI":"10.1038\/nm0303-269"},{"key":"S1462399416000119_ref30","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-36"},{"key":"S1462399416000119_ref117","doi-asserted-by":"crossref","first-page":"7873","DOI":"10.1523\/JNEUROSCI.22-18-07873.2002","article-title":"Non-Fc-mediated mechanisms are involved in clearance of amyloid-\u03b2 in vivo by immunotherapy","volume":"22","author":"Bacskai","year":"2002","journal-title":"Journal of Neuroscience"},{"key":"S1462399416000119_ref84","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00232-5"},{"key":"S1462399416000119_ref12","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.263"},{"key":"S1462399416000119_ref48","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312889"},{"key":"S1462399416000119_ref9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"S1462399416000119_ref63","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10253"},{"key":"S1462399416000119_ref65","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4401-10.2011"},{"key":"S1462399416000119_ref66","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20886"},{"key":"S1462399416000119_ref58","doi-asserted-by":"publisher","DOI":"10.1159\/000354778"},{"key":"S1462399416000119_ref81","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.04.007"},{"key":"S1462399416000119_ref54","doi-asserted-by":"publisher","DOI":"10.1038\/srep09649"},{"key":"S1462399416000119_ref70","doi-asserted-by":"publisher","DOI":"10.2165\/11533070-000000000-00000"},{"key":"S1462399416000119_ref79","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784705487"},{"key":"S1462399416000119_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.02.002"},{"key":"S1462399416000119_ref50","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.3314"},{"key":"S1462399416000119_ref109","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701078200"},{"key":"S1462399416000119_ref116","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00840.x"},{"key":"S1462399416000119_ref125","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1242\/jcs.104.2.521","article-title":"Receptor-mediated endocytosis of transferrin at the blood\u2013brain barrier","volume":"104","author":"Roberts","year":"1993","journal-title":"Journal of Cell Science"},{"key":"S1462399416000119_ref97","doi-asserted-by":"publisher","DOI":"10.1038\/363446a0"},{"key":"S1462399416000119_ref104","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501746200"},{"key":"S1462399416000119_ref96","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2014.07.008"},{"key":"S1462399416000119_ref115","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1090-04.2004"},{"key":"S1462399416000119_ref110","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04426.x"},{"key":"S1462399416000119_ref106","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2724"},{"key":"S1462399416000119_ref113","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.035"},{"key":"S1462399416000119_ref102","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00896-9"},{"key":"S1462399416000119_ref119","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's disease mouse model","volume":"27","author":"Kou","year":"2011","journal-title":"Journal of Alzheimer's Disease"},{"key":"S1462399416000119_ref108","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(92)90065-6"},{"key":"S1462399416000119_ref129","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.10.061"},{"key":"S1462399416000119_ref88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.01.061"},{"key":"S1462399416000119_ref124","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490180206"},{"key":"S1462399416000119_ref95","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.25428"},{"key":"S1462399416000119_ref29","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2013.838555"}],"container-title":["Expert Reviews in Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1462399416000119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T12:59:54Z","timestamp":1656766794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1462399416000119\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":132,"alternative-id":["S1462399416000119"],"URL":"https:\/\/doi.org\/10.1017\/erm.2016.11","relation":{},"ISSN":["1462-3994"],"issn-type":[{"value":"1462-3994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016]]},"article-number":"e13"}}