{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:06:17Z","timestamp":1790960777823,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"am","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R01AG061091"],"award-info":[{"award-number":["R01AG061091"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R56AG055416"],"award-info":[{"award-number":["R56AG055416"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R01AG048349"],"award-info":[{"award-number":["R01AG048349"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&D Transl Res & Clin Interv"],"published-print":{"date-parts":[[2024,10]]},"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n \n Hippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended\u2010release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78\u2010week trial to assess the progression of MCI due to AD. As reported in Mohs et\u00a0al., the decline in the Clinical Dementia Rating Sum of Boxes score (CDR\u2010SB) was reduced by 40% in apolipoprotein E (\n APOE<\/jats:italic>\n ) \u03b54 non\u2010carriers\u00a0over the 78\u2010week duration of the study with a negligible effect in carriers. Here we report an exploratory analysis of the effects of AGB101 on neuroimaging and biomarker measures in the 44\n APOE<\/jats:italic>\n \u03b54 non\u2010carriers who completed the 78\u2010week protocol.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Structural magnetic resonance imaging scans obtained at baseline and after 78 weeks were analyzed using the Automated Segmentation of Hippocampal Subfields software providing volume measures of key structures of the medial temporal lobe relevant to AD progression. Blood samples collected at 78 weeks in the study were analyzed for plasma biomarkers.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Treatment with AGB101 significantly reduced atrophy of the left entorhinal cortex (ERC) compared to placebo. This reduction in atrophy was correlated with\u00a0less decline\u00a0in the CDR\u2010SB score over\u00a078 weeks and with lower neurofilament light chain (NfL), a marker of neurodegeneration.<\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n The HOPE4MCI study showed that\n APOE<\/jats:italic>\n \u03b54 non\u2010carriers treated with AGB101 demonstrated a substantially more favorable treatment effect compared to carriers. Here we report that treatment with AGB101 in non\u2010carriers of\n APOE<\/jats:italic>\n \u03b54 significantly reduced atrophy of the left ERC over 78 weeks. That reduction in atrophy was closely coupled with the change in CDR\u2010SB and with plasma NfL indicative of neurodegeneration in the brain. These exploratory analyses are consistent with a reduction in neurodegeneration in\n APOE<\/jats:italic>\n \u03b54 non\u2010carriers treated with AGB101 before a clinical diagnosis of dementia.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n AGB101 slows entorhinal cortex (ERC) atrophy in apolipoprotein E (\n APOE<\/jats:italic>\n ) \u03b54 non\u2010carriers with mild cognitive impairment (MCI) due to Alzheimer's disease (AD).\n <\/jats:p>\n <\/jats:list-item>\n \n Slowing ERC atrophy by AGB101 is associated with less Clinical Dementia Rating Sum of Boxes decline.<\/jats:p>\n <\/jats:list-item>\n \n Slowing ERC atrophy by AGB101 is associated with lower neurofilament light chain.<\/jats:p>\n <\/jats:list-item>\n \n \n AGB101 treatment reduces neurodegeneration in\n APOE<\/jats:italic>\n \u03b54 non\u2010carriers with MCI due to AD.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/trc2.70004","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T07:00:31Z","timestamp":1728630031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in\n APOE<\/i>\n \u03b54 non\u2010carriers with mild cognitive impairment due to Alzheimer's disease"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-641X","authenticated-orcid":false,"given":"Arnold","family":"Bakker","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA"},{"name":"Department of Psychological and Brain Sciences Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Rani","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mohs","sequence":"additional","affiliation":[{"name":"AgeneBio, Inc. Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences Johns Hopkins University Baltimore Maryland USA"},{"name":"AgeneBio, Inc. Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.05.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20163"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000171450.97464.49"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.207"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.10.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2015.02.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.023"},{"key":"e_1_2_8_9_1","article-title":"The HOPE4MCI study: A randomized double\u2010blind assessment of AGB101 for the treatment of MCI due to AD","volume":"10","author":"Mohs R","year":"2024","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)74869-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1052\u20105149(03)00025\u2010X"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200004)47:4<430::AID-ANA5>3.0.CO;2-I"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00021-6"},{"key":"e_1_2_8_14_1","first-page":"41","article-title":"Entorhinal and transentorhinal atrophy in mild cognitive impairment using longitudinal diffeomorphometry","volume":"9","author":"Tward DJ","year":"2017","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.101617"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00804"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.12.008"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1272946"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12465"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24607"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","unstructured":"YushkevichPA YangGao GerigG.ITK\u2010SNAP: An interactive tool for semi\u2010automatic segmentation of multi\u2010modality biomedical images. in2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).2016:3342\u20103345. 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