{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:11:54Z","timestamp":1783944714019,"version":"3.55.0"},"reference-count":87,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>Reports highlight new Alzheimer's disease treatments using anti-amyloid-\u03b2 immunotherapy, but we see major concerns. The trials supporting lecanemab and donanemab approvals have methodological flaws, and the benefits may be smaller than the minimal clinically important difference\u2014or absent\u2014since patients with poor tolerance were excluded from efficacy analyses. Moreover, treatment increases amyloid-related imaging abnormalities, suggesting local tissue damage, and is linked to brain volume loss. These issues raise doubts about whether regulators are adequately balancing risks and benefits compared to academic critics.<\/jats:p>","DOI":"10.1177\/13872877261417548","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T13:46:02Z","timestamp":1774014362000},"page":"1079-1084","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Serious doubts about amyloid-\u03b2 (A\u03b2) biomarkers and anti-A\u03b2 immunotherapy"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-2367","authenticated-orcid":false,"given":"Poul F.","family":"H\u00f8ilund-Carlsen","sequence":"first","affiliation":[{"name":"Odense University Hospital"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2442-7901","authenticated-orcid":false,"given":"Abass","family":"Alavi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0822-862X","authenticated-orcid":false,"given":"Tommaso","family":"Costa","sequence":"additional","affiliation":[{"name":"University of Turin"},{"name":"University of Turin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael L.","family":"Neve","sequence":"additional","affiliation":[{"name":"Gene Delivery Technology Core, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3300-7420","authenticated-orcid":false,"given":"Mona-Elisabeth","family":"Revheim","sequence":"additional","affiliation":[{"name":"The Intervention Centre, Division of Technology and Innovation, Oslo University Hospital, Oslo, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge R.","family":"Barrio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"e_1_3_3_2_2","article-title":"Dear Scientists, Come Down From Your Ivory Tower","author":"Moses A","unstructured":"Moses A. Dear Scientists, Come Down From Your Ivory Tower. PLOS SciComm, https:\/\/scicomm.plos.org\/2024\/04\/10\/dear-scientists-come-down-from-your-ivory-tower\/ (April 10, 2024, accessed 5 August 2025).","journal-title":"PLOS SciComm"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.07.222"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.11.002"},{"key":"e_1_3_3_5_2","first-page":"146","article-title":"\u00dcber eine eigenartige Erkrankung der Hirnrinde","volume":"64","author":"Alzheimer A","year":"1907","unstructured":"Alzheimer A. \u00dcber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr Psychisch Gerichtl Med 1907; 64: 146\u2013148.","journal-title":"Allg Z Psychiatr Psychisch Gerichtl Med"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02036432"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(84)80190-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.24.8729"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb04000.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1991.tb00667.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720511796717195"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01558"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90609-V"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160612"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology10050394"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00128-X"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12701"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251374319"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.5216"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221365"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4669"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002624"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww159"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.004"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230772"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.add9993"},{"key":"e_1_3_3_33_2","volume-title":"Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's","author":"Piller C","year":"2025","unstructured":"Piller C. Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's. London: Icon Books, 2025."},{"key":"e_1_3_3_34_2","unstructured":"Alzheimer\u2019s Society. Explaining the amyloid research study controversy.https:\/\/www.alzheimers.org.uk\/for-researchers\/explaining-amyloid-research-study-controversy (2022 accessed 6 August 2025)."},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00112-7"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02988-7"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251359642"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70142-4"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190559"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025847118"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.741"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz162"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.08.001"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1185-7"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00933-1"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.06.001"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.003"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-012799"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220841"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073892"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000159740.16984.3C"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000159743.08996.99"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207156"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00813-8"},{"key":"e_1_3_3_60_2","unstructured":"Aducanumab (marketed as Aduhelm) Information. https:\/\/www.fda.gov\/drugs\/postmarket-drug-safety-information-patients-and-providers\/aducanumab-marketed-aduhelm-information (2021 accessed 16 January 2026)."},{"key":"e_1_3_3_61_2","unstructured":"FDA Converts Novel Alzheimer\u2019s Disease Treatment to Traditional Approval. U.S. Food and Drug Administration https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-converts-novel-alzheimers-disease-treatment-traditional-approval.(2023 accessed 7 August 2025)."},{"key":"e_1_3_3_62_2","unstructured":"FDA approves treatment for adults with Alzheimer\u2019s disease. https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-treatment-adults-alzheimers-disease (2024 accessed 7 August 2025)."},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-009-0233-0"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-024-01067-2"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-023-07194-w"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2024.2416947"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004568"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2025.100195"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/hup.70017"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230099"},{"key":"e_1_3_3_71_2","article-title":"Long-term exposure to non-steroidal anti-inflammatory (NSAID) medication in relation to dementia risk: a population-based cohort study","volume":"20","author":"vom Hofe I","year":"2025","unstructured":"vom Hofe I, Stricker BH, Ikram MK, et al. Long-term exposure to non-steroidal anti-inflammatory (NSAID) medication in relation to dementia risk: a population-based cohort study. Alzheimers Dement 2025; 20: e088721.","journal-title":"Alzheimers Dement"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011832"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac096"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000042744"},{"key":"e_1_3_3_75_2","article-title":"Donepezil for dementia due to Alzheimer's disease","volume":"6","author":"Birks JS","year":"2018","unstructured":"Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev 2018; 6: CD001190.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_3_76_2","article-title":"Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis","volume":"2","author":"Battle CE","year":"2021","unstructured":"Battle CE, Abdul-Rahim AH, Shenkin SD. Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis. Cochrane Database Syst Rev 2021; 2: CD013306.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_3_77_2","article-title":"Galantamine for dementia due to Alzheimer's disease and mild cognitive impairment","volume":"11","author":"Lim AWY","year":"2024","unstructured":"Lim AWY, Schneider L, Loy C. Galantamine for dementia due to Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2024; 11: CD001747.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_3_78_2","first-page":"306","article-title":"The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics","volume":"21","author":"Karran E","year":"2022","unstructured":"Karran E, Strooper BD. The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics. Nat Rev 2022; 21: 306\u2013318.","journal-title":"Nat Rev"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215699"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102112"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914499"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170313122937"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210234"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-221286"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220190"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2025.100367"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031914"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.2174\/0115672050403066250904112611"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261417548","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877261417548","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261417548","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:43:19Z","timestamp":1783942999000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877261417548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":87,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1177\/13872877261417548"],"URL":"https:\/\/doi.org\/10.1177\/13872877261417548","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}