{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:42:03Z","timestamp":1792078923305,"version":"4.4.0"},"reference-count":160,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common cause of dementia, pathologically defined by extracellular amyloid-\u03b2 (A\u03b2) plaques and intracellular tau neurofibrillary tangles. Recent U.S. Food and Drug Administration (FDA) approvals of anti-amyloid monoclonal antibodies (mAbs) aducanumab, lecanemab, and donanemab represent the first disease-modifying therapies for early AD. These therapies have generated both optimism and controversy due to modest efficacy and safety concerns, particularly amyloid-related imaging abnormalities (ARIAs). This review synthesizes current evidence on the efficacy, safety, and biomarker-guided use of anti-A\u03b2 mAbs in AD. Methods: We searched PubMed, Scopus, Web of Science, and Google Scholar to 31 July 2025 for studies on anti-amyloid mAbs in AD. Sources included peer-reviewed articles and regulatory reports. The extracted data covered study design, population, amyloid confirmation, dosing, outcomes, biomarkers, ARIA incidence, and management. Results: Anti-amyloid mAbs consistently demonstrated robust amyloid clearance and modest slowing of clinical decline in early symptomatic AD. Differences emerged across agents in efficacy signals, safety profiles, and regulatory outcomes. Lecanemab and donanemab showed more consistent cognitive benefits, while aducanumab yielded mixed findings, leading to its withdrawal. ARIAs were the most frequent adverse events, occurring more often in APOE \u03b54 carriers and typically during early treatment. Biomarker analyses also revealed favorable downstream effects, including reductions in phosphorylated tau and markers of astroglial injury, supporting engagement of disease biology. Conclusions: Anti-amyloid mAbs provide proof of concept for AD modification, with the greatest benefit in early disease stages and moderate tau burden. Optimal use requires biomarker confirmation of the amyloid, careful tau staging, and genetic risk assessment. While limitations remain, these therapies represent a pivotal step toward precision neurology and may serve as a foundation for multimodal strategies targeting tau, neuroinflammation, and vascular pathology.<\/jats:p>","DOI":"10.3390\/jpm15090437","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T10:51:33Z","timestamp":1757933493000},"page":"437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Anti-Amyloid Monoclonal Antibodies for Alzheimer\u2019s Disease: Evidence, ARIA Risk, and Precision Patient Selection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-4780","authenticated-orcid":false,"given":"Amer E.","family":"Alkhalifa","sequence":"first","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Al Mokhlf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Science and Technology, Sana\u2019a 15034, Yemen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande","family":"Ali","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Zonguldak B\u00fclent Ecevit University, Zonguldak 67100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7278-9134","authenticated-orcid":false,"given":"Nour F.","family":"Al-Ghraiybah","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Syropoulou","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1021\/acschemneuro.4c00339","article-title":"Alzheimer\u2019s Disease: Exploring the Landscape of Cognitive Decline","volume":"15","author":"Tenchov","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S1474-4422(11)70072-2","article-title":"The projected effect of risk factor reduction on Alzheimer\u2019s disease prevalence","volume":"10","author":"Barnes","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2024). 2024 Alzheimer\u2019s disease facts and figures. Alzheimers Dement, 20, 3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"ref_5","first-page":"43","article-title":"Alzheimer\u2019s Disease Puzzle: Delving into Pathogenesis Hypotheses","volume":"15","author":"Nasb","year":"2024","journal-title":"Aging Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1093\/brain\/awv316","article-title":"Alzheimer\u2019s disease in the 100 years since Alzheimer\u2019s death","volume":"138","author":"Ryan","year":"2015","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chen, Z.-R., Huang, J.-B., Yang, S.-L., and Hong, F.-F. (2022). Role of cholinergic signaling in Alzheimer\u2019s disease. Molecules, 27.","DOI":"10.3390\/molecules27061816"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/jnnp.66.2.137","article-title":"The cholinergic hypothesis of Alzheimer\u2019s disease: A review of progress","volume":"66","author":"Francis","year":"1999","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: Challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1212\/WNL.0000000000000596","article-title":"Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis","volume":"83","author":"Ryman","year":"2014","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1093\/brain\/awad159","article-title":"The amyloid cascade hypothesis: An updated critical review","volume":"146","author":"Kepp","year":"2023","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","article-title":"New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias","volume":"54","author":"Bellenguez","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Andrade-Guerrero, J., Santiago-Balmaseda, A., Jeronimo-Aguilar, P., Vargas-Rodr\u00edguez, I., Cadena-Su\u00e1rez, A.R., S\u00e1nchez-Garibay, C., Pozo-Molina, G., M\u00e9ndez-Catal\u00e1, C.F., Cardenas-Aguayo, M.D., and Diaz-Cintra, S. (2023). Alzheimer\u2019s Disease: An Updated Overview of Its Genetics. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043754"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S1474-4422(16)00063-6","article-title":"Dementia in Down\u2019s syndrome","volume":"15","author":"Ballard","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The role of apolipoprotein E in Alzheimer\u2019s disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jsps.2022.10.004","article-title":"An update on the novel and approved drugs for Alzheimer disease","volume":"30","author":"Alhazmi","year":"2022","journal-title":"Saudi Pharm. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Miculas, D.C., Negru, P.A., Bungau, S.G., Behl, T., Hassan, S.S.U., and Tit, D.M. (2022). Pharmacotherapy Evolution in Alzheimer\u2019s Disease: Current Framework and Relevant Directions. Cells, 12.","DOI":"10.3390\/cells12010131"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Thawabteh, A.M., Ghanem, A.W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., and Karaman, R. (2024). Recent Advances in Therapeutics for the Treatment of Alzheimer\u2019s Disease. Molecules, 29.","DOI":"10.3390\/molecules29215131"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00570","DOI":"10.1016\/j.neurot.2025.e00570","article-title":"Maximizing the benefit and managing the risk of anti-amyloid monoclonal antibody therapy for Alzheimer\u2019s disease: Strategies and research directions","volume":"22","author":"Cummings","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40259-023-00633-2","article-title":"Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer\u2019s Disease","volume":"38","author":"Cummings","year":"2024","journal-title":"BioDrugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3233\/JAD-220046","article-title":"Safety and Efficacy of Monoclonal Antibodies for Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials","volume":"87","author":"Lacorte","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1370\/afm.3050","article-title":"Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis","volume":"22","author":"Ebell","year":"2024","journal-title":"Ann. Fam. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12474","DOI":"10.1002\/trc2.12474","article-title":"Quantitative systems pharmacology-based exploration of relevant anti-amyloid therapy challenges in clinical practice","volume":"10","author":"Geerts","year":"2024","journal-title":"Alzheimer\u2019s Dement"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.2967\/jnumed.125.270152","article-title":"Imaging and fluid biomarkers of Alzheimer disease: Complementation rather than competition","volume":"66","author":"Drzezga","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sato, K., Niimi, Y., Ihara, R., Suzuki, K., Iwata, A., and Iwatsubo, T. (2024). APOE-\u03b54 allele[s]-associated adverse events reported from placebo arm in clinical trials for Alzheimer\u2019s disease: Implications for anti-amyloid beta therapy. Front. Dement., 2.","DOI":"10.3389\/frdem.2023.1320329"},{"key":"ref_29","unstructured":"Kane, M. (2024). Lecanemab therapy and APOE genotype, Medical Genetics Summaries [Internet]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0896-6273(91)90052-2","article-title":"The molecular pathology of Alzheimer\u2019s disease","volume":"6","author":"Selkoe","year":"1991","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0165-6147(91)90609-V","article-title":"Amyloid deposition as the central event in the aetiology of Alzheimer\u2019s disease","volume":"12","author":"Hardy","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.cell.2005.02.008","article-title":"Twenty years of the Alzheimer\u2019s disease amyloid hypothesis: A genetic perspective","volume":"120","author":"Tanzi","year":"2005","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/352239a0","article-title":"Formation of \u03b2-amyloid protein deposits in brains of transgenic mice","volume":"352","author":"Quon","year":"1991","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1212\/01.wnl.0000219668.47116.e6","article-title":"Neuropathology of older persons without cognitive impairment from two community-based studies","volume":"66","author":"Bennett","year":"2006","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1001\/archneurol.2010.179","article-title":"Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people","volume":"67","author":"Shapiro","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1001\/archneur.64.3.noc60123","article-title":"Cerebrospinal fluid tau\/\u03b2-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults","volume":"64","author":"Fagan","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1212\/01.wnl.0000326146.60732.d6","article-title":"Imaging amyloid deposition in Lewy body diseases","volume":"71","author":"Gomperts","year":"2008","journal-title":"Neurology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1523\/JNEUROSCI.1698-16.2016","article-title":"Large Soluble Oligomers of Amyloid \u03b2-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate","volume":"37","author":"Yang","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm1782","article-title":"Amyloid-beta protein dimers isolated directly from Alzheimer\u2019s brains impair synaptic plasticity and memory","volume":"14","author":"Shankar","year":"2008","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1073\/pnas.96.9.5274","article-title":"Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer\u2019s disease","volume":"96","author":"Knowles","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nature06616","article-title":"Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer\u2019s disease","volume":"451","author":"Prada","year":"2008","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/256495a0","article-title":"Continuous cultures of fused cells secreting antibody of predefined specificity","volume":"256","author":"Milstein","year":"1975","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chi, X.-K., Xu, X.-L., Chen, B.-Y., Su, J., and Du, Y.-Z. (2023). Combining nanotechnology with monoclonal antibody drugs for rheumatoid arthritis treatments. J. Nanobiotechnology, 21.","DOI":"10.1186\/s12951-023-01857-8"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zahavi, D., and Weiner, L. (2020). Monoclonal antibodies in cancer therapy. Antibodies, 9.","DOI":"10.3390\/antib9030034"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0140-6736(00)01034-5","article-title":"Therapeutic monoclonal antibodies","volume":"355","author":"Breedveld","year":"2000","journal-title":"Lancet"},{"key":"ref_47","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."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-025-00465-w","article-title":"Second-generation anti-amyloid monoclonal antibodies for Alzheimer\u2019s disease: Current landscape and future perspectives","volume":"14","author":"Kim","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1056\/NEJMoa1705971","article-title":"Trial of Solanezumab for Mild Dementia Due to Alzheimer\u2019s Disease","volume":"378","author":"Honig","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13195-017-0318-y","article-title":"A phase III randomized trial of gantenerumab in prodromal Alzheimer\u2019s disease","volume":"9","author":"Ostrowitzki","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1001\/jamaneurol.2022.2909","article-title":"Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults with Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials","volume":"79","author":"Ostrowitzki","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/14712598.2024.2325551","article-title":"More failure with solanezumab\u2014This time in preclinical Alzheimer\u2019s disease","volume":"24","author":"Doggrell","year":"2024","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103949","DOI":"10.1016\/j.mcn.2024.103949","article-title":"Lecanemab demonstrates highly selective binding to A\u03b2 protofibrils isolated from Alzheimer\u2019s disease brains","volume":"130","author":"Johannesson","year":"2024","journal-title":"Mol. Cell Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Khartabil, N., and Awaness, A. (2025). Targeting Amyloid Pathology in Early Alzheimer\u2019s: The Promise of Donanemab-Azbt. Pharm, 13.","DOI":"10.3390\/pharmacy13010023"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.2174\/0929867331666230727103553","article-title":"Aducanumab in Alzheimer\u2019s Disease: A Critical Update","volume":"31","author":"Ashique","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1093\/brain\/awad188","article-title":"Amyloid-related imaging abnormalities (ARIA): Radiological, biological and clinical characteristics","volume":"146","author":"Hampel","year":"2023","journal-title":"Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"534","DOI":"10.14283\/jpad.2021.52","article-title":"Immunotherapy for Alzheimer\u2019s disease: Current scenario and future perspectives","volume":"8","author":"Usman","year":"2021","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bougea, A., and Gourzis, P. (2024). Biomarker-Based Precision Therapy for Alzheimer\u2019s Disease: Multidimensional Evidence Leading a New Breakthrough in Personalized Medicine. J. Clin. Med., 13.","DOI":"10.3390\/jcm13164661"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Arndt, J.W., Qian, F., Smith, B.A., Quan, C., Kilambi, K.P., Bush, M.W., Walz, T., Pepinsky, R.B., Bussi\u00e8re, T., and Hamann, S. (2018). Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-\u03b2. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-24501-0"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature19323","article-title":"The antibody aducanumab reduces A\u03b2 plaques in Alzheimer\u2019s disease","volume":"537","author":"Sevigny","year":"2016","journal-title":"Nature"},{"key":"ref_61","unstructured":"Biogen (2022). Biogen and Eisai Amend Collaboration Agreements on Alzheimer\u2019s Disease Treatments, Biogen. Available online: https:\/\/investors.biogen.com\/news-releases\/news-release-details\/biogen-and-eisai-amend-collaboration-agreements-alzheimers."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"797","DOI":"10.2147\/CIA.S325026","article-title":"Role of Aducanumab in the Treatment of Alzheimer\u2019s Disease: Challenges and Opportunities","volume":"17","author":"Vaz","year":"2022","journal-title":"Clin. Interv. Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-med-051022-043645","article-title":"Lessons learned from approval of aducanumab for Alzheimer\u2019s disease","volume":"75","author":"Heidebrink","year":"2024","journal-title":"Annu. Rev. Med."},{"key":"ref_64","unstructured":"Padda, I.S., and Parmar, M. (2024). Aducanumab. StatPearls, StatPearls Publishing."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e069780","DOI":"10.1136\/bmj-2021-069780","article-title":"Regulatory decisions diverge over aducanumab for Alzheimer\u2019s disease","volume":"376","author":"Lythgoe","year":"2022","journal-title":"BMJ"},{"key":"ref_66","unstructured":"Laura Joszt, M. (2024). Biogen abandons aducanumab, pivots focus to Lecanemab for alzheimer disease. Am. J. Manag. Care."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"197","DOI":"10.14283\/jpad.2022.30","article-title":"Two randomized phase 3 studies of aducanumab in early Alzheimer\u2019s disease","volume":"9","author":"Aisen","year":"2022","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_68","unstructured":"Belluck, P., and Robbins, R. (2021). Three FDA advisers resign over agency\u2019s approval of Alzheimer\u2019s drug. N. Y. Times, 11."},{"key":"ref_69","unstructured":"Lin, G.A., Whittington, M.D., Synnott, P.G., McKenna, A., Campbell, J., Pearson, S.D., and Rind, D.M. (2021). Aducanumab for Alzheimer\u2019s disease: Effectiveness and value; final evidence report and meeting summary. Inst. Clin. Econ. Rev., 5."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/j.1471-4159.2007.04759.x","article-title":"Sensitive ELISA detection of amyloid-\u03b2 protofibrils in biological samples","volume":"103","author":"Englund","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nn0901-887","article-title":"The\u2019Arctic\u2019APP mutation (E693G) causes Alzheimer\u2019s disease by enhanced A\u03b2 protofibril formation","volume":"4","author":"Nilsberth","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_72","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":"J. Alzheimer\u2019s Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13195-016-0181-2","article-title":"Safety and tolerability of BAN2401\u2014A clinical study in Alzheimer\u2019s disease with a protofibril selective A\u03b2 antibody","volume":"8","author":"Logovinsky","year":"2016","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13195-021-00813-8","article-title":"A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer\u2019s disease with lecanemab, an anti-A\u03b2 protofibril antibody","volume":"13","author":"Swanson","year":"2021","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s40120-022-00350-y","article-title":"Long-Term Health Outcomes of Lecanemab in Patients with Early Alzheimer\u2019s Disease Using Simulation Modeling","volume":"11","author":"Tafazzoli","year":"2022","journal-title":"Neurol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_77","unstructured":"U.S. Food and Drug Administration FDA Converts Novel Alzheimer\u2019s Disease Treatment to Traditional Approval; [updated 6 July 2023]; FDA: Silver Spring, MD, USA, 2023, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-converts-novel-alzheimers-disease-treatment-traditional-approval."},{"key":"ref_78","unstructured":"Eisai, Inc. (2023). Leqembi\u2122 (lecanemab-irmb) Prescribing Information, Eisai Inc.. Available online: https:\/\/www.leqembi.com."},{"key":"ref_79","unstructured":"Eisai, B. (2023). FDA Approves LEQEMBI\u2122 (Lecanemab-Irmb) Under the Accelerated Approval Pathway for the Treatment of Alzheimer\u2019s Disease, Biogen. Available online: https:\/\/investors.biogen.com\/news-releases\/news-release-details\/fda-approves-leqembitm-lecanemab-irmb-under-accelerated-approval."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10-24926","DOI":"10.24926\/iip.v15i1.5787","article-title":"Lecanemab: A second in class therapy for the management of early Alzheimer\u2019s disease","volume":"15","author":"Yoon","year":"2024","journal-title":"Innov. Pharm."},{"key":"ref_81","unstructured":"Eli Lilly and Company (2024). Lilly\u2019s Kisunla\u2122 (Donanemab-azbt) Approved by the FDA for the Treatment of Early Symptomatic Alzheimer\u2019s Disease, Eli Lilly and Company. Available online: https:\/\/investor.lilly.com\/news-releases\/news-release-details\/lillys-kisunlatm-donanemab-azbt-approved-fda-treatment-early."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.neuron.2012.10.029","article-title":"A plaque-specific antibody clears existing \u03b2-amyloid plaques in Alzheimer\u2019s disease mice","volume":"76","author":"Demattos","year":"2012","journal-title":"Neuron"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"100150","DOI":"10.1016\/j.tjpad.2025.100150","article-title":"Donanemab: Appropriate use recommendations","volume":"12","author":"Rabinovici","year":"2025","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_84","unstructured":"Eli Lilly and Company (2024). A Study of LY3002813 in Participants with Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT01837641."},{"key":"ref_85","unstructured":"Eli Lilly and Company A Study of LY3002813 in Participants with Memory Damage Due to Alzheimer\u2019s Disease (AD) or AD; ClinicalTrials.gov: Bethesda, MD, USA, 2025. [Completed Clinical Trial Investigating LY3002813 (Donanemab) in Alzheimer\u2019s Disease], Available online: https:\/\/clinicaltrials.gov\/study\/NCT02624778."},{"key":"ref_86","unstructured":"Eli Lilly and Company (2022). A Study of LY3002813 in Participants with Early Symptomatic Alzheimer\u2019s Disease (TRAILBLAZER-ALZ), Available online: https:\/\/clinicaltrials.gov\/study\/NCT03367403."},{"key":"ref_87","unstructured":"Eli Lilly and Company (2025). A Study of Donanemab (LY3002813) in Participants with Early Alzheimer\u2019s Disease (TRAILBLAZER-ALZ 2), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04437511."},{"key":"ref_88","unstructured":"Eli Lilly and Company (2025). A Donanemab (LY3002813) Study in Participants with Preclinical Alzheimer\u2019s Disease (TRAILBLAZER-ALZ 3), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05026866."},{"key":"ref_89","unstructured":"Eli Lilly and Company (2024). A Study of Donanemab (LY3002813) Compared with Aducanumab in Participants with Early Symptomatic Alzheimer\u2019s Disease (TRAILBLAZER-ALZ 4), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05108922."},{"key":"ref_90","unstructured":"Eli Lilly and Company (2025). A Study of Donanemab (LY3002813) in Participants with Early Symptomatic Alzheimer\u2019s Disease (TRAILBLAZER-ALZ 5), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05508789."},{"key":"ref_91","unstructured":"Eli Lilly and Company (2025). A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults with Early Alzheimer\u2019s Disease (TRAILBLAZER-ALZ 6); ClinicalTrials.gov Identifier: NCT05738486, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05738486."},{"key":"ref_92","unstructured":"(2021). International Collaboration for Real-World Evidence in Alzheimer\u2019s Disease (ICARE AD)\u2014A Prospective Real-World Observational Study of Aducanumab-Avwa in Patients with Alzheimer\u2019s Disease in the US, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05097131."},{"key":"ref_93","unstructured":"(2015). A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects with Early Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT02477800."},{"key":"ref_94","unstructured":"(2022). A Phase 3b\/4 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants with Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05310071."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1001\/jamaneurol.2022.2793","article-title":"Association of Amyloid Reduction After Donanemab Treatment with Tau Pathology and Clinical Outcomes: The TRAILBLAZER-ALZ Randomized Clinical Trial","volume":"79","author":"Shcherbinin","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_96","unstructured":"(2019). A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study with an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects with Early Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03887455."},{"key":"ref_97","unstructured":"(2013). A Placebo-Controlled, Double-Blind, Parallel-Group, Bayesian Adaptive Randomization Design and Dose Regimen-Finding Study With an Open-Label Extension Phase to Evaluate Safety, Tolerability and Efficacy of BAN2401 in Subjects with Early Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT01767311."},{"key":"ref_98","unstructured":"(2010). A Randomized, Double-blind, Placebo-controlled, Combined Single Ascending Dose and Multiple Ascending Dose Study to Assess Safety, Tolerability, Immunogenicity, Pharmacodynamic Response, and Pharmacokinetics of Intravenous Infusions of BAN2401 in Subjects with Mild to Moderate Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT01230853."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13195-024-01412-z","article-title":"The search for clarity regarding \u201cclinically meaningful outcomes\u201d in Alzheimer disease clinical trials: CLARITY-AD and Beyond","volume":"16","author":"Tarawneh","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"507","DOI":"10.14283\/jpad.2022.41","article-title":"Clinical trial endpoints and their clinical meaningfulness in early stages of Alzheimer\u2019s disease","volume":"9","author":"Cohen","year":"2022","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/ana.410310303","article-title":"Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention","volume":"31","author":"Berg","year":"1992","journal-title":"Ann. Neurol."},{"key":"ref_102","unstructured":"Rogers, B.M. No Easy Answers on Clinical Meaningfulness of Alzheimer\u2019s Treatments. Alzforum. Available online: https:\/\/www.alzforum.org\/news\/research-news\/no-easy-answers-clinical-meaningfulness-alzheimers-treatments."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.dadm.2016.11.004","article-title":"Assessing quality of life in Alzheimer\u2019s disease: Implications for clinical trials","volume":"6","author":"Ye","year":"2017","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monitoring."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.jalz.2014.01.007","article-title":"Taking stock: A multistakeholder perspective on improving the delivery of care and the development of treatments for Alzheimer\u2019s disease","volume":"11","author":"Bradley","year":"2015","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_106","unstructured":"Alzheimer\u2019s Research UK AAIC 2025: The Future of Alzheimer\u2019s Research Is Here. Alzheimer\u2019s Research UK News, 2025. Available online: https:\/\/alzheimersresearchuk.org\/news\/aaic-2025-the-future-of-alzheimers-research-is-here\/."},{"key":"ref_107","unstructured":"Eli Lilly and Company Lilly\u2019s Kisunla (donanemab-azbt) Showed Growing Benefit over Three Years in Early Symptomatic Alzheimer\u2019s Disease. Eli Lilly and Company: Indianapolis, IN, USA, 2025. Available online: https:\/\/investor.lilly.com\/news-releases\/news-release-details\/lillys-kisunla-donanemab-azbt-showed-growing-benefit-over-three."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3348\/kjr.2024.0105","article-title":"Amyloid-related imaging abnormalities in the era of anti-amyloid beta monoclonal antibodies for Alzheimer\u2019s disease: Recent updates on clinical and imaging features and MRI monitoring","volume":"25","author":"Jeong","year":"2024","journal-title":"Korean J. Radiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jamaneurol.2021.5205","article-title":"Amyloid-Related Imaging Abnormalities and \u03b2-Amyloid-Targeting Antibodies: A Systematic Review","volume":"79","author":"Filippi","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10571-016-0334-7","article-title":"The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline","volume":"36","author":"Corriveau","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/brain\/awh379","article-title":"Abeta-related angiitis: Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy","volume":"128","author":"Scolding","year":"2005","journal-title":"Brain"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/ana.10810","article-title":"Clinical manifestations of cerebral amyloid angiopathy-related inflammation","volume":"55","author":"Eng","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1080\/14737175.2025.2526113","article-title":"Contemporary perspectives in cerebral amyloid angiopathy","volume":"25","author":"Sellimi","year":"2025","journal-title":"Expert. Rev. Neurother."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41582-019-0281-2","article-title":"Cerebral amyloid angiopathy and Alzheimer disease\u2014One peptide, two pathways","volume":"16","author":"Greenberg","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.biopsych.2017.08.010","article-title":"Anti-Amyloid-\u03b2 Monoclonal Antibodies for Alzheimer\u2019s Disease: Pitfalls and Promise","volume":"83","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"E19","DOI":"10.3174\/ajnr.A7586","article-title":"Amyloid-Related Imaging Abnormalities with Emerging Alzheimer Disease Therapeutics: Detection and Reporting Recommendations for Clinical Practice","volume":"43","author":"Cogswell","year":"2022","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Crespi, G.A., Hermans, S.J., Parker, M.W., and Miles, L.A. (2015). Molecular basis for mid-region amyloid-\u03b2 capture by leading Alzheimer\u2019s disease immunotherapies. Sci. Rep., 5.","DOI":"10.1038\/srep09649"},{"key":"ref_119","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":"Salloway","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3233\/JAD-160216","article-title":"Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer\u2019s Disease Patients","volume":"57","author":"Ketter","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_121","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":"Doody","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.trci.2017.04.003","article-title":"Multiple-dose ponezumab for mild-to-moderate Alzheimer\u2019s disease: Safety and efficacy","volume":"3","author":"Landen","year":"2017","journal-title":"Alzheimer\u2019s Dement"},{"key":"ref_123","unstructured":"Biogen, Inc. Lecanemab Confirmatory Phase 3 Clarity AD Study Met Primary Endpoint, Showing Statistically Significant Results in Early Alzheimer\u2019s Disease. Available online: https:\/\/investors.biogen.com\/news-releases\/news-release-details\/lecanemab-confirmatory-phase-3-clarity-ad-study-met-primary."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trci.2016.06.002","article-title":"First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer\u2019s disease","volume":"2","author":"Ferrero","year":"2016","journal-title":"Alzheimer\u2019s Dement"},{"key":"ref_125","first-page":"e12101","article-title":"Symptomatic amyloid-related imaging abnormalities in an APOE \u03b54\/\u03b54 patient treated with aducanumab","volume":"12","author":"VandeVrede","year":"2020","journal-title":"Alzheimer\u2019s Dement"},{"key":"ref_126","unstructured":"Food and Drug Administration (FDA) Aducanumab (marketed as Aduhelm) Information, Available online: https:\/\/www.fda.gov\/drugs\/postmarket-drug-safety-information-patients-and-providers\/aducanumab-marketed-aduhelm-information."},{"key":"ref_127","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":"Sperling","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_128","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_129","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. Alzheimer\u2019s Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.neulet.2010.02.016","article-title":"Amyloid load in nondemented brains correlates with APOE e4","volume":"473","author":"Caselli","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e230009","DOI":"10.1148\/rg.230009","article-title":"Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-\u03b2 Therapy","volume":"43","author":"Agarwal","year":"2023","journal-title":"Radiographics"},{"key":"ref_132","first-page":"106","article-title":"Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer\u2019s disease treated with bapineuzumab: A historical, prospective secondary analysis","volume":"87","author":"Arrighi","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1148\/radiol.2211001712","article-title":"Suppression of cerebrospinal fluid and blood flow artifacts in FLAIR MR imaging with a single-slab three-dimensional pulse sequence: Initial experience","volume":"221","author":"Kallmes","year":"2001","journal-title":"Radiology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"211","DOI":"10.14283\/jpad.2022.21","article-title":"Detection and management of amyloid-related imaging abnormalities in patients with Alzheimer\u2019s disease treated with anti-amyloid beta therapy","volume":"9","author":"Barakos","year":"2022","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Withington, C.G., and Turner, R.S. (2022). Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer\u2019s Disease. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.862369"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"362","DOI":"10.14283\/jpad.2023.30","article-title":"Lecanemab: Appropriate use recommendations","volume":"10","author":"Cummings","year":"2023","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_137","first-page":"563","article-title":"Donanemab for Alzheimer\u2019s Disease: From Preclinical Research to the Clinical Application","volume":"25","author":"Dodel","year":"2025","journal-title":"Expert Rev. Neurother."},{"key":"ref_138","unstructured":"Alzheimer\u2019s Association (2024). Donanemab for Early-Stage Alzheimer\u2019s Disease: Recommendations for Clinical Practice, Alzheimer\u2019s Association. Available online: https:\/\/pro.alz.org\/files\/download\/DBB34343-2D0C-42BF-9101-42A32583CA37.pdf."},{"key":"ref_139","unstructured":"Europe, A. (2025). Clinical and Research Experts Respond to the EMA Refusal of Donanemab in a Letter to the Lancet Editors Luxembourg, Alzheimer Europe. Available online: https:\/\/www.alzheimer-europe.org\/news\/clinical-and-research-experts-respond-ema-refusal-donanemab-letter-lancet-editors?language_content_entity=en#:~:text=Gothenburg%2C%20Sweden,ALZ%206."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/S0140-6736(25)00833-5","article-title":"The regulatory rollercoaster continues\u2014EMA refuses donanemab","volume":"405","author":"Haass","year":"2025","journal-title":"Lancet"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s00415-025-13131-y","article-title":"FDA vs. EMA: Evaluating donanemab and the global debate on accelerated approvals","volume":"272","author":"Pokhrel","year":"2025","journal-title":"J. Neurol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Mahase, E. (2021). Aducanumab: European agency rejects Alzheimer\u2019s drug over efficacy and safety concerns. Br. Med. J. Publ. Group, 375.","DOI":"10.1136\/bmj.n3127"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"E1430","DOI":"10.1503\/cmaj.211134","article-title":"Should Canadian patients look forward to aducanumab for Alzheimer disease?","volume":"193","author":"Watt","year":"2021","journal-title":"Can. Med. Assoc. J."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Tanzi, R.E. (2021). FDA Approval of Aduhelm Paves a New Path for Alzheimer\u2019s Disease, ACS Publications.","DOI":"10.1021\/acschemneuro.1c00394"},{"key":"ref_145","unstructured":"Gurud, T., Jadhav, M., Bhosale, A., Wadkar, S., Balid, A., Fulari, S., and Narawade, T. (2024). Lecanemab: A Novel Therapeutic Approach for Alzheimer\u2019s Disease. Int. J. Sci. Res. Technol., 1."},{"key":"ref_146","unstructured":"Agency, E.M. (2024). Leqembi Recommended for Treatment of Early Alzheimer\u2019s Disease, European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/news\/leqembi-recommended-treatment-early-alzheimers-disease#:~:text=After%20re%2Dexamining%20its%20initial,patients%20with%20early%20Alzheimer\u2019s%20disease."},{"key":"ref_147","unstructured":"Wall, J. Results from Lilly\u2019s Landmark Phase 3 Trial of Donanemab Presented. Eli Lilly and Company: Indianapolis, IN, USA, 2023. Available online: https:\/\/investor.lilly.com\/news-releases\/news-release-details\/results-lillys-landmark-phase-3-trial-donanemab-presented."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"353","DOI":"10.14283\/jpad.2023.41","article-title":"Clinical implementation of lecanemab: Challenges, questions and solutions","volume":"10","author":"Iwatsubo","year":"2023","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1254\/fpj.24005","article-title":"Mechanism of action and clinical trial results of Lecanemab (Leqembi\u00ae 200 mg, 500 mg for Intravenous Infusion), a novel treatment for Alzheimer\u2019s disease","volume":"159","author":"Niidome","year":"2024","journal-title":"Folia Pharmacol. Jpn."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s41983-025-00968-3","article-title":"Amyloid solutions: Lecanemab, gantenerumab, and donanemab in the treatment of Alzheimer\u2019s disease","volume":"61","author":"Ameen","year":"2025","journal-title":"Egypt. J. Neurol. Psychiatry Neurosurg."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/0166-2236(93)90078-Z","article-title":"Tau protein and the neurofibrillary pathology of Alzheimer\u2019s disease","volume":"16","author":"Goedert","year":"1993","journal-title":"Trends Neurosci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Feigin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Parhizkar, S., and Holtzman, D.M. (2022). APOE mediated neuroinflammation and neurodegeneration in Alzheimer\u2019s disease. Seminars in Immunology, Elsevier.","DOI":"10.1016\/j.smim.2022.101594"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"107839","DOI":"10.1016\/j.celrep.2020.107839","article-title":"Caspase activation and caspase-mediated cleavage of APP is associated with amyloid \u03b2-protein-induced synapse loss in Alzheimer\u2019s disease","volume":"31","author":"Park","year":"2020","journal-title":"Cell Rep."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","article-title":"Donanemab in Early Alzheimer\u2019s Disease","volume":"384","author":"Mintun","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1001\/jamaneurol.2022.3392","article-title":"Association of donanemab treatment with exploratory plasma biomarkers in early symptomatic Alzheimer disease: A secondary analysis of the TRAILBLAZER-ALZ randomized clinical trial","volume":"79","author":"Pontecorvo","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/ana.21953","article-title":"Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease","volume":"67","author":"Vemuri","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.jmb.2019.01.045","article-title":"Microglia in Alzheimer\u2019s Disease: Exploring How Genetics and Phenotype Influence Risk","volume":"431","author":"McQuade","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_159","unstructured":"Eisai Co., Ltd Eisai\u2019s Approach to U.S. Pricing for Leqembi\u2122 (Lecanemab), a Treatment for Early Alzheimer\u2019s Disease, Sets Forth Our Concept of \u201cSocietal Value of Medicine\u201d in Relation to \u201cPrice of Medicine.\u201d 2023. Available online: https:\/\/media-us.eisai.com\/2023-01-06-EISAIS-APPROACH-TO-U-S-PRICING-FOR-LEQEMBI-TM-LECANEMAB-,-A-TREATMENT-FOR-EARLY-ALZHEIMERS-DISEASE,-SETS-FORTH-OUR-CONCEPT-OF-SOCIETAL-VALUE-OF-MEDICINE-IN-RELATION-TO-PRICE-OF-MEDICINE#:~:text=This%20yearly%20estimate%20of%20$37%2C600,pricing%20may%20vary%20by%20patient."},{"key":"ref_160","unstructured":"Medicare, C., and Services, C.f.M. (2022). Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer\u2019s Disease (AD), Available online: https:\/\/www.cms.gov\/medicare\/coverage\/coverage-evidence-development\/monoclonal-antibodies-directed-against-amyloid-treatment-alzheimers-disease-ad."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/9\/437\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:45:44Z","timestamp":1760035544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/9\/437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":160,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jpm15090437"],"URL":"https:\/\/doi.org\/10.3390\/jpm15090437","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]}}}