{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:29:41Z","timestamp":1780525781414,"version":"3.54.1"},"reference-count":63,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100018578","name":"Clinical and Translational Science Institute, Boston University","doi-asserted-by":"publisher","award":["1UL1TR001430"],"award-info":[{"award-number":["1UL1TR001430"]}],"id":[{"id":"10.13039\/100018578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["E01HT9425-23-1-1058"],"award-info":[{"award-number":["E01HT9425-23-1-1058"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK133940"],"award-info":[{"award-number":["R01DK133940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03AG063255"],"award-info":[{"award-number":["R03AG063255"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Boston University Evans Center","award":["2024 B4D-ARC Award"],"award-info":[{"award-number":["2024 B4D-ARC Award"]}]},{"DOI":"10.13039\/100007161","name":"Boston University","doi-asserted-by":"publisher","award":["2023 Ignition Award"],"award-info":[{"award-number":["2023 Ignition Award"]}],"id":[{"id":"10.13039\/100007161","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007161","name":"Boston University","doi-asserted-by":"publisher","award":["Undergraduate Research Opportunity Program"],"award-info":[{"award-number":["Undergraduate Research Opportunity Program"]}],"id":[{"id":"10.13039\/100007161","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Slit Guidance Ligand 2 (SLIT2) binds Roundabout (ROBO) guidance receptors to direct axon pathfinding and neuron migration during nervous system development. SLIT2 expression has previously been linked to dementia risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To study the association between SLIT2 expression in human vitreous humor and plasma samples and neurocognitive test scores in a cross-sectional cohort study utilizing a novel, highly-sensitive Meso Scale Discovery (MSD) assay for SLIT2 detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventy-nine individuals with a mean age of 55.79\u2009\u00b1\u200912.03 years underwent eye surgery with collection of vitreous humor, blood (plasma) collection, and neurocognitive assessment. Vitreous humor and plasma samples were analyzed by SLIT2 MSD electrochemiluminescence immunoassay. Associations between SLIT2 levels in vitreous humor and plasma were analyzed using GraphPad Prism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found up to a 7-fold higher level of SLIT2 in human vitreous humor compared to plasma. Lower vitreous SLIT2 levels were associated with a lower Montreal Cognitive Assessment (MoCA) score and Immediate Recall Verbatim (IRV) z-score, and higher plasma SLIT2 was associated with a lower MoCA score. In multivariate analysis using single and multiple predictor models, the same significant associations were found when adjusted for age, sex, race, diabetic status, diabetic retinopathy status, glaucoma status, and Apolipoprotein E (\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      ) genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SLIT2 protein levels are significantly associated with MoCA score and IRV z-score in middle-aged individuals. The relationship remained significant when adjusted for demographics, co-morbidity, and\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      genotype, suggesting SLIT2 may be a sensitive biomarker for detection of mild cognitive impairment and early dementia, and warrants further studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251374287","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:36:36Z","timestamp":1756906596000},"page":"1555-1566","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The association between SLIT2 in human vitreous humor and plasma and neurocognitive test scores"],"prefix":"10.1177","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7873-0569","authenticated-orcid":false,"given":"Sara I","family":"Shoushtari","sequence":"first","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7157-986X","authenticated-orcid":false,"given":"Easton","family":"Liaw","sequence":"additional","affiliation":[{"name":"Boston University Sargent College of Health and Rehabilitation Sciences, Boston, MA, USA"},{"name":"Nephrology Section, Department of Medicine, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreevardhan","family":"Alluri","sequence":"additional","affiliation":[{"name":"Ophthalmology and Vision Science, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Ophthalmology and Vision Science, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-1306","authenticated-orcid":false,"given":"Sudhir","family":"Kumar","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Nephrology Section, Department of Medicine, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Huynh","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Nephrology Section, Department of Medicine, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-6570","authenticated-orcid":false,"given":"Insa M","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Nephrology Section, Department of Medicine, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5843-9476","authenticated-orcid":false,"given":"Steven","family":"Ness","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Ophthalmology and Vision Science, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-0152","authenticated-orcid":false,"given":"Xuejing","family":"Chen","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Ophthalmology and Vision Science, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3523-8225","authenticated-orcid":false,"given":"Nicole H","family":"Siegel","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Ophthalmology and Vision Science, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-326X","authenticated-orcid":false,"given":"Sushrut S","family":"Waikar","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Nephrology Section, Department of Medicine, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6954-4477","authenticated-orcid":false,"given":"Thor D","family":"Stein","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer's Disease and CTE Center, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston, MA, USA"},{"name":"Department of Veterans Affairs Medical Center, VA Boston Healthcare System, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-3044","authenticated-orcid":false,"given":"Weining","family":"Lu","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Nephrology Section, Department of Medicine, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0061-098X","authenticated-orcid":false,"given":"Manju L","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Ophthalmology and Vision Science, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2019-205952"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01148-5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028035"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2020.04.021"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202300225"},{"key":"e_1_3_4_7_2","first-page":"97","article-title":"Pathophysiology and classification of neurodegenerative diseases","volume":"15","author":"Relja M","year":"2004","unstructured":"Relja M. Pathophysiology and classification of neurodegenerative diseases. EJIFCC 2004; 15: 97\u201399.","journal-title":"EJIFCC"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2022.07.010"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180060"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033118"},{"key":"e_1_3_4_11_2","unstructured":"Thorpe KE Levey AI Thomas J. U.S. Burden of neurodegenerative disease: Literature review summary. from partnership to fight chronic disease https:\/\/www.fightchronicdisease.org\/sites\/default\/files\/May%202021%20Neurodegenerative%20Disease%20Burden%20on%20US%20-%20FINAL%20.pdf. (2021)"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2017.01.005"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.5694\/mja2.51849"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1159\/000525639"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.3746"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35766-w"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11070980"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40208-x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01556-y"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-181104"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230167"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00677-4"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3233\/ADR-210283"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3849"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.31877"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.132829"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-020-05100-7"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2008.06.003"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2007.12.017"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.09.034"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdev.2021.203677"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072165"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2020.1766445"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02311-2"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.12.015"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00384-6"},{"key":"e_1_3_4_37_2","article-title":"Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies","volume":"374","author":"Kivim\u00e4ki M","year":"2021","unstructured":"Kivim\u00e4ki M, Walker KA, Pentti J, et al. Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies. Br Med J 2021; 374: n1804.","journal-title":"Br Med J"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.053"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185795"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S377430"},{"key":"e_1_3_4_41_2","first-page":"101","article-title":"Neuropsychological evaluations in adults","volume":"99","author":"Schroeder RW","year":"2019","unstructured":"Schroeder RW, Martin PK, Walling A. Neuropsychological evaluations in adults. Am Fam Physician 2019; 99: 101\u2013108.","journal-title":"Am Fam Physician"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000223"},{"key":"e_1_3_4_43_2","unstructured":"Neuropsychological Battery Tests reported on Form C2 Uniform Data Set (UDS) v3.0 www.alz.washington.edu (2006)."},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14279-8"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-180"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.1.100"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12816"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00070-3"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112812"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1159\/000369933"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800259"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02935-2"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141215"},{"key":"e_1_3_4_56_2","first-page":"1935","article-title":"Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain","volume":"42","author":"Li G","year":"2018","unstructured":"Li G, He X, Li H, et al. Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain. Int J Mol Med 2018; 42: 1935\u20131944.","journal-title":"Int J Mol Med"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav0618"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2016.10.024"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2017.32.3.383"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.889505"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21579"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(23)00211-8"},{"key":"e_1_3_4_63_2","article-title":"Environmental and lifestyle risk factors for early-onset dementia: a systematic review","volume":"93","author":"Bosi M","year":"2022","unstructured":"Bosi M, Malavolti M, Garuti C, et al. Environmental and lifestyle risk factors for early-onset dementia: a systematic review. Acta Biomed 2022; 93: e2022336.","journal-title":"Acta Biomed"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1340608"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251374287","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877251374287","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251374287","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251374287","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:11:44Z","timestamp":1777371104000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877251374287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1177\/13872877251374287"],"URL":"https:\/\/doi.org\/10.1177\/13872877251374287","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.05.03.652072","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]}}}