{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:31:19Z","timestamp":1790937079907,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Drug Investig"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1007\/s40261-023-01331-1","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T13:02:42Z","timestamp":1702558962000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Lecanemab: More Questions Than Answers!"],"prefix":"10.1007","volume":"44","author":[{"given":"Upinder","family":"Kaur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Tiwari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasanka","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-0016","authenticated-orcid":false,"given":"Sankha Shubhra","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"1331_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.31887\/DCNS.2009.11.2\/cqiu","volume":"11","author":"C Qiu","year":"2009","unstructured":"Qiu C, Kivipelto M, von Strauss E. Epidemiology of Alzheimer\u2019s disease: occurrence, determinants, and strategies toward intervention. Dialog Clin Neurosci. 2009;11:111\u201328.","journal-title":"Dialog Clin Neurosci"},{"key":"1331_CR2","first-page":"1","volume":"8","author":"X-X Zhang","year":"2021","unstructured":"Zhang X-X, Tian Y, Wang Z-T, Ma Y-H, Tan L, Yu J-T. The epidemiology of Alzheimer\u2019s disease modifiable risk factors and prevention. J Prev Alzheimers Dis. 2021;8:1\u20139.","journal-title":"J Prev Alzheimers Dis."},{"key":"1331_CR3","doi-asserted-by":"publisher","first-page":"2898","DOI":"10.1002\/alz.12928","volume":"19","author":"J Lee","year":"2023","unstructured":"Lee J, Meijer E, Langa KM, Ganguli M, Varghese M, Banerjee J, et al. Prevalence of dementia in India: national and state estimates from a nationwide study. Alzheimers Dement. 2023;19:2898\u2013912.","journal-title":"Alzheimers Dement"},{"key":"1331_CR4","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.2174\/1567205013666160603004239","volume":"13","author":"SS Chakrabarti","year":"2016","unstructured":"Chakrabarti SS, Bir A, Poddar J, Sinha M, Ganguly A, Chakrabarti S. Ceramide and sphingosine-1-phosphate in cell death pathways: relevance to the pathogenesis of Alzheimer\u2019s disease. Curr Alzheimer Res. 2016;13:1232\u201348.","journal-title":"Curr Alzheimer Res"},{"key":"1331_CR5","unstructured":"US Food and Drug Administration. Leqembi\u2122 (lecanemab-irmb) injection, for intravenous use full prescribing information. 2023. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761269s000lbl.pdf. Accessed 18 Apr 2023."},{"key":"1331_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.870517","volume":"14","author":"M Shi","year":"2022","unstructured":"Shi M, Chu F, Zhu F, Zhu J. Impact of anti-amyloid-\u03b2 monoclonal antibodies on the pathology and clinical profile of Alzheimer\u2019s disease: a focus on aducanumab and lecanemab. Front Aging Neurosci. 2022;14: 870517.","journal-title":"Front Aging Neurosci."},{"key":"1331_CR7","unstructured":"US Food and Drug Administration. FDA grants accelerated approval for Alzheimer\u2019s disease treatment. 2023. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-grants-accelerated-approval-alzheimers-disease-treatment. Accessed 18 Apr 2023."},{"key":"1331_CR8","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1001\/jama.2022.24494","volume":"329","author":"HD Larkin","year":"2023","unstructured":"Larkin HD. Lecanemab gains FDA approval for early Alzheimer disease. JAMA. 2023;329:363.","journal-title":"JAMA"},{"key":"1331_CR9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s13311-022-01308-6","volume":"20","author":"L S\u00f6derberg","year":"2022","unstructured":"S\u00f6derberg L, Johannesson M, Nygren P, Laudon H, Eriksson F, Osswald G, et al. Lecanemab, aducanumab, and gantenerumab - binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for Alzheimer\u2019s disease. Neurotherapeutics. 2022;20:195\u2013206.","journal-title":"Neurotherapeutics."},{"key":"1331_CR10","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s13195-022-01124-2","volume":"14","author":"E McDade","year":"2022","unstructured":"McDade E, Cummings JL, Dhadda S, Swanson CJ, Reyderman L, Kanekiyo M, et al. Lecanemab in patients with early Alzheimer\u2019s disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022;14:191.","journal-title":"Alzheimers Res Ther."},{"key":"1331_CR11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/alzrt246","volume":"6","author":"L Lannfelt","year":"2014","unstructured":"Lannfelt L, M\u00f6ller C, Basun H, Osswald G, Sehlin D, Satlin A, et al. Perspectives on future Alzheimer therapies: amyloid-\u03b2 protofibrils: a new target for immunotherapy with BAN2401 in Alzheimer\u2019s disease. Alzheimers Res Ther. 2014;6:16.","journal-title":"Alzheimers Res Ther."},{"key":"1331_CR12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13195-016-0181-2","volume":"8","author":"V Logovinsky","year":"2016","unstructured":"Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, et al. Safety and tolerability of BAN2401: a clinical study in Alzheimer\u2019s disease with a protofibril selective A\u03b2 antibody. Alzheimers Res Ther. 2016;8:14.","journal-title":"Alzheimers Res Ther."},{"key":"1331_CR13","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13195-021-00813-8","volume":"13","author":"CJ Swanson","year":"2021","unstructured":"Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer\u2019s disease with lecanemab, an anti-A\u03b2 protofibril antibody. Alzheimers Res Ther. 2021;13:80.","journal-title":"Alzheimers Res Ther."},{"key":"1331_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer\u2019s disease. N Engl J Med. 2023;388:9\u201321.","journal-title":"N Engl J Med"},{"key":"1331_CR15","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/d41586-023-00030-3","volume":"613","author":"S Reardon","year":"2023","unstructured":"Reardon S. FDA approves Alzheimer\u2019s drug lecanemab amid safety concerns. Nature. 2023;613:227\u20138.","journal-title":"Nature"},{"key":"1331_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2023.100657","volume":"29","author":"L J\u00f6nsson","year":"2023","unstructured":"J\u00f6nsson L, Wimo A, Handels R, Johansson G, Boada M, Engelborghs S, et al. The affordability of lecanemab, an amyloid-targeting therapy for Alzheimer\u2019s disease: an EADC-EC viewpoint. Lancet Reg Health Eur. 2023;29: 100657.","journal-title":"Lancet Reg Health Eur."},{"key":"1331_CR17","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1016\/S0140-6736(22)02480-1","volume":"400","author":"T Lancet","year":"2022","unstructured":"The Lancet. Lecanemab for Alzheimer\u2019s disease: tempering hype and hope. Lancet. 2022;400:1899.","journal-title":"Lancet"},{"key":"1331_CR18","unstructured":"US Food and Drug Administration. FDA converts novel Alzheimer\u2019s disease treatment to traditional approval. 2023. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-converts-novel-alzheimers-disease-treatment-traditional-approval#:~:text=Leqembi%20is%20the%20first%20amyloid,pathophysiological%20feature%20of%20the%20disease. Accessed 16 Nov 2023."},{"key":"1331_CR19","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12883-017-0850-1","volume":"17","author":"AI Abushouk","year":"2017","unstructured":"Abushouk AI, Elmaraezy A, Aglan A, Salama R, Fouda S, Fouda R, et al. Bapineuzumab for mild to moderate Alzheimer\u2019s disease: a meta-analysis of randomized controlled trials. BMC Neurol. 2017;17:66.","journal-title":"BMC Neurol"},{"key":"1331_CR20","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1056\/NEJMoa1304839","volume":"370","author":"S Salloway","year":"2014","unstructured":"Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer\u2019s disease. N Engl J Med. 2014;370:322\u201333.","journal-title":"N Engl J Med"},{"key":"1331_CR21","first-page":"106","volume":"87","author":"HM Arrighi","year":"2016","unstructured":"Arrighi HM, Barakos J, Barkhof F, Tampieri D, Jack C, Melan\u00e7on D, et al. Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer\u2019s disease treated with bapineuzumab: a historical, prospective secondary analysis. J Neurol Neurosurg Psychiatry. 2016;87:106\u201312.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1331_CR22","first-page":"197","volume":"9","author":"S Budd Haeberlein","year":"2022","unstructured":"Budd Haeberlein S, Aisen PS, Barkhof F, Chalkias S, Chen T, Cohen S, et al. Two randomized phase 3 studies of aducanumab in early Alzheimer\u2019s disease. J Prev Alzheimers Dis. 2022;9:197\u2013210.","journal-title":"J Prev Alzheimers Dis."},{"key":"1331_CR23","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.3233\/JAD-140864","volume":"43","author":"J Ni","year":"2014","unstructured":"Ni J, Auriel E, Martinez-Ramirez S, Keil B, Reed AK, Fotiadis P, et al. Cortical localization of microbleeds in cerebral amyloid angiopathy: an ultra high-field 7T MRI study. J Alzheimers Dis. 2014;43:1325\u201330.","journal-title":"J Alzheimers Dis"},{"key":"1331_CR24","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1111\/jch.13606","volume":"21","author":"S Elmst\u00e5hl","year":"2019","unstructured":"Elmst\u00e5hl S, Ellstr\u00f6m K, Siennicki-Lantz A, Abul-Kasim K. Association between cerebral microbleeds and hypertension in the Swedish general population \u201cGood Aging in Sk\u00e5ne\u201d study. J Clin Hypertension. 2019;21:1099\u2013107.","journal-title":"J Clin Hypertension."},{"key":"1331_CR25","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00401-016-1580-y","volume":"132","author":"M Shinohara","year":"2016","unstructured":"Shinohara M, Murray ME, Frank RD, Shinohara M, DeTure M, Yamazaki Y, et al. Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer\u2019s disease. Acta Neuropathol. 2016;132:225\u201334.","journal-title":"Acta Neuropathol"},{"key":"1331_CR26","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1056\/NEJMoa1705971","volume":"378","author":"LS Honig","year":"2018","unstructured":"Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, et al. Trial of solanezumab for mild dementia due to Alzheimer\u2019s disease. N Engl J Med. 2018;378:321\u201330.","journal-title":"N Engl J Med"},{"key":"1331_CR27","unstructured":"Piller C. Second death linked to potential antibody treatment for Alzheimer\u2019s disease. Sci News. 2022. https:\/\/www.science.org\/content\/article\/second-death-linked-potential-antibody-treatment-alzheimer-s-disease. Accessed 19 Apr 2023."},{"key":"1331_CR28","unstructured":"Piller C. Scientists tie third clinical trial death to experimental Alzheimer\u2019s drug. Sci News. 2022. https:\/\/www.science.org\/content\/article\/scientists-tie-third-clinical-trial-death-experimental-alzheimer-s-drug. Accessed 19 Apr 2023."},{"key":"1331_CR29","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1056\/NEJMc2215148","volume":"388","author":"NJ Reish","year":"2023","unstructured":"Reish NJ, Jamshidi P, Stamm B, Flanagan ME, Sugg E, Tang M, et al. Multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke. N Engl J Med. 2023;388:478\u20139.","journal-title":"N Engl J Med"},{"key":"1331_CR30","unstructured":"Public Relations Department ECo, Ltd. Article regarding safety information of lecanemab reported by ScienceInsider. 2022. https:\/\/www.eisai.com\/news\/2022\/pdf\/enews202292pdf.pdf. Accessed 15 Oct 2023."},{"key":"1331_CR31","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/nn.4017","volume":"18","author":"K Herrup","year":"2015","unstructured":"Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18:794\u20139.","journal-title":"Nat Neurosci"},{"key":"1331_CR32","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.jalz.2017.09.011","volume":"14","author":"Y An","year":"2018","unstructured":"An Y, Varma VR, Varma S, Casanova R, Dammer E, Pletnikova O, et al. Evidence for brain glucose dysregulation in Alzheimer\u2019s disease. Alzheimers Dement. 2018;14:318\u201329.","journal-title":"Alzheimers Dement"},{"key":"1331_CR33","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.3233\/JAD-160841","volume":"55","author":"L Szablewski","year":"2016","unstructured":"Szablewski L. Glucose transporters in brain: in health and in Alzheimer\u2019s disease. J Alzheimers Dis. 2016;55:1307\u201320.","journal-title":"J Alzheimers Dis"},{"key":"1331_CR34","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13024-020-00376-6","volume":"15","author":"W Wang","year":"2020","unstructured":"Wang W, Zhao F, Ma X, Perry G, Zhu X. Mitochondria dysfunction in the pathogenesis of Alzheimer\u2019s disease: recent advances. Mol Neurodegener. 2020;15:30.","journal-title":"Mol Neurodegener"},{"key":"1331_CR35","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","volume":"17","author":"F Leng","year":"2021","unstructured":"Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17:157\u201372.","journal-title":"Nat Rev Neurol"},{"key":"1331_CR36","doi-asserted-by":"publisher","first-page":"282","DOI":"10.14336\/AD.2014.002","volume":"6","author":"S Chakrabarti","year":"2015","unstructured":"Chakrabarti S, Kumar Khemka V, Banerjee A, Chatterjee G, Ganguly A, Biswas A. Metabolic risk factors of sporadic Alzheimer\u2019s disease: implications in the pathology, pathogenesis and treatment. Aging Dis. 2015;6:282.","journal-title":"Aging Dis"},{"key":"1331_CR37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13195-019-0512-1","volume":"11","author":"Y-N Ou","year":"2019","unstructured":"Ou Y-N, Xu W, Li J-Q, Guo Y, Cui M, Chen K-L, et al. FDG-PET as an independent biomarker for Alzheimer\u2019s biological diagnosis: a longitudinal study. Alzheimers Res Ther. 2019;11:57.","journal-title":"Alzheimers Res Ther."},{"key":"1331_CR38","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3233\/JAD-140741","volume":"43","author":"S Tucker","year":"2014","unstructured":"Tucker S, M\u00f6ller C, Tegerstedt K, Lord A, Laudon H, Sj\u00f6dahl J, et al. The murine version of BAN2401 (mAb158) selectively reduces amyloid-\u03b2 protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2014;43:575\u201388.","journal-title":"J Alzheimers Dis"},{"key":"1331_CR39","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.nbd.2009.08.007","volume":"36","author":"A Lord","year":"2009","unstructured":"Lord A, Gumucio A, Englund H, Sehlin D, Sundquist VS, S\u00f6derberg L, et al. An amyloid-\u03b2 protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer\u2019s disease. Neurobiol Dis. 2009;36:425\u201334.","journal-title":"Neurobiol Dis"},{"key":"1331_CR40","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/j.1755-5949.2010.00177.x","volume":"17","author":"R Medeiros","year":"2011","unstructured":"Medeiros R, Baglietto-Vargas D, LaFerla FM. The role of Tau in Alzheimer\u2019s disease and related disorders. CNS Neurosci Ther. 2011;17:514\u201324.","journal-title":"CNS Neurosci Ther"}],"container-title":["Clinical Drug Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-023-01331-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40261-023-01331-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-023-01331-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T12:32:05Z","timestamp":1704457925000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40261-023-01331-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,14]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["1331"],"URL":"https:\/\/doi.org\/10.1007\/s40261-023-01331-1","relation":{},"ISSN":["1173-2563","1179-1918"],"issn-type":[{"value":"1173-2563","type":"print"},{"value":"1179-1918","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,14]]},"assertion":[{"value":"20 November 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No sources of funding were used for the preparation of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Upinder Kaur, Jaideep Reddy, Ashutosh Tiwari, Sasanka Chakrabarti, and Sankha Shubhra Chakrabarti have no conflicts of interest that are directly relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interests"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Conceptualization: UK, SSC, AT; investigation: UK, SSC, JR, SC; writing, original draft preparation: SSC, UK, AT, JR, SC; writing, review and editing: SSC. All authors read and approved the final version.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 contributions"}}]}}