{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T13:17:33Z","timestamp":1794662253594,"version":"4.9.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Alector, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1038\/s41591-026-04273-1","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:02:17Z","timestamp":1772704937000},"page":"1708-1716","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The TREM2 agonistic antibody AL002 in early Alzheimer\u2019s disease: a phase 2 randomized trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-0803","authenticated-orcid":false,"given":"Catherine J.","family":"Mummery","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J.","family":"Mayorga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany W.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brady","family":"Burgess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubrahmanyam","family":"Budda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovingly Quitania","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Kenkare-Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derk D.","family":"Purcell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Salloway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grundman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0212-4643","authenticated-orcid":false,"given":"Giacomo","family":"Salvadore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"4273_CR1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr.","year":"2018","unstructured":"Jack, C. R. Jr. et al. NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 14, 535\u2013562 (2018).","journal-title":"Alzheimers Dement."},{"key":"4273_CR2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","volume":"179","author":"JM Long","year":"2019","unstructured":"Long, J. M. & Holtzman, D. M. Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179, 312\u2013339 (2019).","journal-title":"Cell"},{"key":"4273_CR3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","volume":"330","author":"JR Sims","year":"2023","unstructured":"Sims, J. R. et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 330, 512\u2013527 (2023).","journal-title":"JAMA"},{"key":"4273_CR4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck, C. H. et al. Lecanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 388, 9\u201321 (2023).","journal-title":"N. Engl. J. Med."},{"key":"4273_CR5","doi-asserted-by":"crossref","DOI":"10.1016\/j.neurot.2025.e00570","volume":"22","author":"JL Cummings","year":"2025","unstructured":"Cummings, J. L. Maximizing the benefit and managing the risk of anti-amyloid monoclonal antibody therapy for Alzheimer\u2019s disease: strategies and research directions. Neurotherapeutics 22, e00570 (2025).","journal-title":"Neurotherapeutics"},{"key":"4273_CR6","doi-asserted-by":"crossref","first-page":"578342","DOI":"10.1016\/j.jneuroim.2024.578342","volume":"390","author":"S Fruhwurth","year":"2024","unstructured":"Fruhwurth, S., Zetterberg, H. & Paludan, S. R. Microglia and amyloid plaque formation in Alzheimer\u2019s disease \u2212 evidence, possible mechanisms, and future challenges. J. Neuroimmunol. 390, 578342 (2024).","journal-title":"J. Neuroimmunol."},{"key":"4273_CR7","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13024-022-00588-y","volume":"17","author":"J Hou","year":"2022","unstructured":"Hou, J., Chen, Y., Grajales-Reyes, G. & Colonna, M. TREM2 dependent and independent functions of microglia in Alzheimer\u2019s disease. Mol. Neurodegener. 17, 84 (2022).","journal-title":"Mol. Neurodegener."},{"key":"4273_CR8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa1211851","volume":"368","author":"R Guerreiro","year":"2013","unstructured":"Guerreiro, R. et al. TREM2 variants in Alzheimer\u2019s disease. N. Engl. J. Med. 368, 117\u2013127 (2013).","journal-title":"N. Engl. J. Med."},{"key":"4273_CR9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa1211103","volume":"368","author":"T Jonsson","year":"2013","unstructured":"Jonsson, T. et al. Variant of TREM2 associated with the risk of Alzheimer\u2019s disease. N. Engl. J. Med. 368, 107\u2013116 (2013).","journal-title":"N. Engl. J. Med."},{"key":"4273_CR10","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.neuron.2018.01.031","volume":"97","author":"Y Zhao","year":"2018","unstructured":"Zhao, Y. et al. TREM2 is a receptor for \u03b2-amyloid that mediates microglial function. Neuron 97, 1023\u20131031 (2018).","journal-title":"Neuron"},{"key":"4273_CR11","doi-asserted-by":"crossref","first-page":"26043","DOI":"10.1074\/jbc.M115.679043","volume":"290","author":"Y Atagi","year":"2015","unstructured":"Atagi, Y. et al. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J. Biol. Chem. 290, 26043\u201326050 (2015).","journal-title":"J. Biol. Chem."},{"key":"4273_CR12","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.neuron.2016.06.015","volume":"91","author":"FL Yeh","year":"2016","unstructured":"Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C. & Sheng, M. TREM2 binds to apolipoproteins, including APOE and CLU\/APOJ, and thereby facilitates uptake of amyloid-beta by microglia. Neuron 91, 328\u2013340 (2016).","journal-title":"Neuron"},{"key":"4273_CR13","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.cell.2015.01.049","volume":"160","author":"Y Wang","year":"2015","unstructured":"Wang, Y. et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer\u2019s disease model. Cell 160, 1061\u20131071 (2015).","journal-title":"Cell"},{"key":"4273_CR14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13024-018-0298-9","volume":"13","author":"M Gratuze","year":"2018","unstructured":"Gratuze, M., Leyns, C. E. G. & Holtzman, D. M. New insights into the role of TREM2 in Alzheimer\u2019s disease. Mol. Neurodegener. 13, 66 (2018).","journal-title":"Mol. Neurodegener."},{"key":"4273_CR15","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","volume":"217","author":"DV Hansen","year":"2018","unstructured":"Hansen, D. V., Hanson, J. E. & Sheng, M. Microglia in Alzheimer\u2019s disease. J. Cell Biol. 217, 459\u2013472 (2018).","journal-title":"J. Cell Biol."},{"key":"4273_CR16","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.neuron.2016.05.003","volume":"90","author":"P Yuan","year":"2016","unstructured":"Yuan, P. et al. TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 90, 724\u2013739 (2016).","journal-title":"Neuron"},{"key":"4273_CR17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13024-018-0262-8","volume":"13","author":"PJ Cheng-Hathaway","year":"2018","unstructured":"Cheng-Hathaway, P. J. et al. The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer\u2019s disease. Mol. Neurodegener. 13, 29 (2018).","journal-title":"Mol. Neurodegener."},{"key":"4273_CR18","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1523\/JNEUROSCI.2110-16.2016","volume":"37","author":"TR Jay","year":"2017","unstructured":"Jay, T. R. et al. Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer\u2019s disease. J. Neurosci. 37, 637\u2013647 (2017).","journal-title":"J. Neurosci."},{"key":"4273_CR19","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer\u2019s disease. Cell 169, 1276\u20131290 (2017).","journal-title":"Cell"},{"key":"4273_CR20","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.neuron.2018.02.002","volume":"97","author":"CYD Lee","year":"2018","unstructured":"Lee, C. Y. D. et al. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathological phenotypes in Alzheimer\u2019s disease models. Neuron 97, 1032\u20131048 (2018).","journal-title":"Neuron"},{"key":"4273_CR21","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201911227","volume":"12","author":"K Schlepckow","year":"2020","unstructured":"Schlepckow, K. et al. Enhancing protective microglial activities with a dual function TREM2 antibody to the stalk region. EMBO Mol. Med. 12, e11227 (2020).","journal-title":"EMBO Mol. Med."},{"key":"4273_CR22","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-020-01915-0","volume":"17","author":"BR Price","year":"2020","unstructured":"Price, B. R. et al. Therapeutic Trem2 activation ameliorates amyloid-beta deposition and improves cognition in the 5XFAD model of amyloid deposition. J. Neuroinflammation 17, 238 (2020).","journal-title":"J. Neuroinflammation"},{"key":"4273_CR23","doi-asserted-by":"crossref","unstructured":"Wang, S. et al. Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer\u2019s disease model. J. Exp. Med. 217, e20200785 (2020).","DOI":"10.1084\/jem.20200785"},{"key":"4273_CR24","doi-asserted-by":"crossref","unstructured":"Jain, N., Lewis, C. A., Ulrich, J. D. & Holtzman, D. M. Chronic TREM2 activation exacerbates A\u03b2-associated tau seeding and spreading. J. Exp. Med. 220, e20220654 (2023).","DOI":"10.1084\/jem.20220654"},{"key":"4273_CR25","doi-asserted-by":"crossref","unstructured":"Etxeberria, A. et al. Neutral or detrimental effects of TREM2 agonist antibodies in preclinical models of Alzheimer\u2019s disease and multiple sclerosis. J. Neurosci. 44, e2347232024 (2024).","DOI":"10.1523\/JNEUROSCI.2347-23.2024"},{"key":"4273_CR26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s13195-024-01599-1","volume":"16","author":"H Long","year":"2024","unstructured":"Long, H. et al. Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer\u2019s disease. Alzheimers Res. Ther. 16, 235 (2024).","journal-title":"Alzheimers Res. Ther."},{"key":"4273_CR27","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/s41591-021-01369-8","volume":"27","author":"S Salloway","year":"2021","unstructured":"Salloway, S. et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer\u2019s disease. Nat. Med. 27, 1187\u20131196 (2021).","journal-title":"Nat. Med."},{"key":"4273_CR28","volume":"8","author":"G Wang","year":"2022","unstructured":"Wang, G. et al. Proportional constrained longitudinal data analysis models for clinical trials in sporadic Alzheimer\u2019s disease. Alzheimers Dement. (N Y) 8, e12286 (2022).","journal-title":"Alzheimers Dement. (N Y)"},{"key":"4273_CR29","doi-asserted-by":"crossref","first-page":"362","DOI":"10.14283\/jpad.2023.30","volume":"10","author":"J Cummings","year":"2023","unstructured":"Cummings, J. et al. Lecanemab: appropriate use recommendations. J. Prev. Alzheimers Dis. 10, 362\u2013377 (2023).","journal-title":"J. Prev. Alzheimers Dis."},{"key":"4273_CR30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1001\/jamaneurol.2021.4161","volume":"79","author":"S Salloway","year":"2022","unstructured":"Salloway, S. et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 79, 13\u201321 (2022).","journal-title":"JAMA Neurol."},{"key":"4273_CR31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1001\/jamaneurol.2024.3937","volume":"82","author":"S Salloway","year":"2025","unstructured":"Salloway, S. et al. Amyloid-related imaging abnormalities (ARIA) in clinical trials of gantenerumab in early Alzheimer disease. JAMA Neurol. 82, 19\u201329 (2025).","journal-title":"JAMA Neurol."},{"key":"4273_CR32","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1084\/jem.20171529","volume":"215","author":"WM Song","year":"2018","unstructured":"Song, W. M. et al. Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J. Exp. Med. 215, 745\u2013760 (2018).","journal-title":"J. Exp. Med."},{"key":"4273_CR33","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.neuron.2019.06.010","volume":"103","author":"A Griciuc","year":"2019","unstructured":"Griciuc, A. et al. TREM2 acts downstream of CD33 in modulating microglial pathology in Alzheimer\u2019s disease. Neuron 103, 820\u2013835 (2019).","journal-title":"Neuron"},{"key":"4273_CR34","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1001\/jamaneurol.2021.3671","volume":"78","author":"AL Benedet","year":"2021","unstructured":"Benedet, A. L. et al. Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum. JAMA Neurol. 78, 1471\u20131483 (2021).","journal-title":"JAMA Neurol."},{"key":"4273_CR35","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s13195-023-01314-6","volume":"15","author":"B Dubois","year":"2023","unstructured":"Dubois, B., von Arnim, C. A. F., Burnie, N., Bozeat, S. & Cummings, J. Biomarkers in Alzheimer\u2019s disease: role in early and differential diagnosis and recognition of atypical variants. Alzheimers Res. Ther. 15, 175 (2023).","journal-title":"Alzheimers Res. Ther."},{"key":"4273_CR36","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41582-021-00520-w","volume":"17","author":"H Hampel","year":"2021","unstructured":"Hampel, H. et al. Developing the ATX(N) classification for use across the Alzheimer disease continuum. Nat. Rev. Neurol. 17, 580\u2013589 (2021).","journal-title":"Nat. Rev. Neurol."},{"key":"4273_CR37","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1038\/s41591-025-03617-7","volume":"31","author":"K Horie","year":"2025","unstructured":"Horie, K. et al. Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer\u2019s disease. Nat. Med. 31, 2044\u20132053 (2025).","journal-title":"Nat. Med."},{"key":"4273_CR38","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","volume":"384","author":"MA Mintun","year":"2021","unstructured":"Mintun, M. A. et al. Donanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 384, 1691\u20131704 (2021).","journal-title":"N. Engl. J. Med."},{"key":"4273_CR39","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s40265-024-02067-8","volume":"84","author":"JA Hey","year":"2024","unstructured":"Hey, J. A. et al. Effects of oral ALZ-801\/valiltramiprosate on plasma biomarkers, brain hippocampal volume, and cognition: results of 2-year single-arm, open-label, phase 2 trial in APOE4 carriers with early Alzheimer\u2019s disease. Drugs 84, 811\u2013823 (2024).","journal-title":"Drugs"},{"key":"4273_CR40","volume":"20","author":"AJ Mayorga","year":"2025","unstructured":"Mayorga, A. J. et al. Baseline characteristics for INVOKE-2: a phase 2 randomized, double-blind, placebo-controlled study evaluating AL002 in early Alzheimer\u2019s disease. Alzheimers Dement. 20, e095594 (2025).","journal-title":"Alzheimers Dement."},{"key":"4273_CR41","doi-asserted-by":"crossref","first-page":"1326784","DOI":"10.3389\/fnins.2024.1326784","volume":"18","author":"SJ Doran","year":"2024","unstructured":"Doran, S. J. & Sawyer, R. P. Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications. Front. Neurosci. 18, 1326784 (2024).","journal-title":"Front. Neurosci."},{"key":"4273_CR42","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1001\/jamaneurol.2025.0065","volume":"82","author":"JA Zimmer","year":"2025","unstructured":"Zimmer, J. A. et al. Amyloid-related imaging abnormalities with donanemab in early symptomatic Alzheimer disease: secondary analysis of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials. JAMA Neurol. 82, 461\u2013469 (2025).","journal-title":"JAMA Neurol."},{"key":"4273_CR43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13024-024-00758-0","volume":"19","author":"X Taylor","year":"2024","unstructured":"Taylor, X. et al. Amyloid-\u03b2 (A\u03b2) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer\u2019s disease. Mol. Neurodegener. 19, 77 (2024).","journal-title":"Mol. Neurodegener."},{"key":"4273_CR44","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S1474-4422(24)00335-1","volume":"23","author":"CRS Belder","year":"2024","unstructured":"Belder, C. R. S. et al. Brain volume change following anti-amyloid \u03b2 immunotherapy for Alzheimer\u2019s disease: amyloid-removal-related pseudo-atrophy. Lancet Neurol. 23, 1025\u20131034 (2024).","journal-title":"Lancet Neurol."},{"key":"4273_CR45","volume":"12","author":"TH Edwin","year":"2020","unstructured":"Edwin, T. H. et al. A high cerebrospinal fluid soluble TREM2 level is associated with slow clinical progression of Alzheimer\u2019s disease. Alzheimers Dement. (Amst.) 12, e12128 (2020).","journal-title":"Alzheimers Dement. (Amst.)"},{"key":"4273_CR46","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.immuni.2023.06.016","volume":"56","author":"L Zhong","year":"2023","unstructured":"Zhong, L. et al. TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity 56, 1794\u20131808 (2023).","journal-title":"Immunity"},{"key":"4273_CR47","volume":"10","author":"L Zhong","year":"2019","unstructured":"Zhong, L. et al. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer\u2019s disease model. Nat. Commun. 10, 1365 (2019).","journal-title":"Nat. Commun."},{"key":"4273_CR48","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2613::AID-IMMU2613>3.0.CO;2-J","volume":"29","author":"KL Armour","year":"1999","unstructured":"Armour, K. L., Clark, M. R., Hadley, A. G. & Williamson, L. M. Recombinant human IgG molecules lacking Fc\u03b3 receptor I binding and monocyte triggering activities. Eur. J. Immunol. 29, 2613\u20132624 (1999).","journal-title":"Eur. J. Immunol."},{"key":"4273_CR49","doi-asserted-by":"crossref","first-page":"e1002344","DOI":"10.1371\/journal.pbio.1002344","volume":"14","author":"RN de Jong","year":"2016","unstructured":"de Jong, R. N. et al. A novel platform for the potentiation of therapeutic antibodies based on antigen-dependent formation of IgG hexamers at the cell surface. PLoS Biol. 14, e1002344 (2016).","journal-title":"PLoS Biol."},{"key":"4273_CR50","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1001\/archneur.65.8.1091","volume":"65","author":"SE O\u2019Bryant","year":"2008","unstructured":"O\u2019Bryant, S. E. et al. Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer\u2019s research consortium study. Arch. Neurol. 65, 1091\u20131095 (2008).","journal-title":"Arch. Neurol."},{"key":"4273_CR51","first-page":"227","volume":"2","author":"AM Wessels","year":"2015","unstructured":"Wessels, A. M. et al. A combined measure of cognition and function for clinical trials: the Integrated Alzheimer\u2019s Disease Rating Scale (iADRS). J. Prev. Alzheimers Dis. 2, 227\u2013241 (2015).","journal-title":"J. Prev. Alzheimers Dis."},{"key":"4273_CR52","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.trci.2019.05.007","volume":"5","author":"AJ Schwarz","year":"2019","unstructured":"Schwarz, A. J. et al. Magnetic resonance imaging measures of brain atrophy from the EXPEDITION3 trial in mild Alzheimer\u2019s disease. Alzheimers Dement. (N Y) 5, 328\u2013337 (2019).","journal-title":"Alzheimers Dement. (N Y)"},{"key":"4273_CR53","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.media.2007.06.004","volume":"12","author":"BB Avants","year":"2008","unstructured":"Avants, B. B., Epstein, C. L., Grossman, M. & Gee, J. C. Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med. Image Anal. 12, 26\u201341 (2008).","journal-title":"Med. Image Anal."},{"key":"4273_CR54","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.trci.2015.03.001","volume":"1","author":"RE Kennedy","year":"2015","unstructured":"Kennedy, R. E., Cutter, G. R., Wang, G. & Schneider, L. S. Using baseline cognitive severity for enriching Alzheimer\u2019s disease clinical trials: how does Mini-Mental State Examination predict rate of change? Alzheimers Dement. (N Y) 1, 46\u201352 (2015).","journal-title":"Alzheimers Dement. (N Y)"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04273-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04273-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04273-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:03:30Z","timestamp":1779285810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04273-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["4273"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04273-1","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"assertion":[{"value":"29 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.J.M. was the principal investigator for INVOKE-2. She is supported by the National Institute for Health and Care Research Biomedical Research Centre at University College London Hospital. She has provided consultancy to Alector, Biogen, Eisai, Ionis, Lilly, Merck Sharp & Dohme, Neurimmune, Novartis, Prevail, Roche\/Genentech and Wave. She has received honoraria for teaching and education from Biogen, Eisai and Lilly. She has received an academic funding award and research support from Biogen. A.J.M., A.S., B. Burgess, T.N., J.G., B. Budda, L.Q.P., R.G., C.L., A.R. and G.S. are employees of Alector, LLC, and may have an equity interest in Alector, Inc. T.W.C., S.K.-M., R.P., M.W. and G.R. were employees of Alector at the time of manuscript conception and may have an equity interest in Alector, Inc. L.S. and D.D.P. have nothing to disclose. S.S. has provided consultation to Eisai, Biogen, Lilly, Roche, Genentech, Novo Nordisk, Prothena, Bristol Myers Squibb, Acumen, Alector, Kisbee, Neurophet, Johnson & Johnson and AbbVie and has pending stock options from Neurophet. Butler Hospital receives research support for clinical trials from Janssen, Lilly, Eisai, Genentech, Roche and Biogen. M.G. is an employee of Global R&D Partners, LLC, which received consulting fees from Alector, Cognition Therapeutics and Genentech.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}