{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:52:12Z","timestamp":1787827932195,"version":"build-2784847793"},"reference-count":60,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Aging","award":["R01 AG075884"],"award-info":[{"award-number":["R01 AG075884"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study is to assess the association between NLR and AD as a biomarker or potential causal step for AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cohorts used for analysis include the UK Biobank (n\u2009=\u2009207100; n\u2009=\u20092198 AD cases) and the All of Us research program (AoU, n\u2009=\u200945202; n\u2009=\u2009263 AD cases) which allowed for a larger sample size than most previous studies. Cox proportional hazard models were used to assess the association between NLR and AD, including in models adjusting for factors in the UK Biobank Dementia Risk Score. A Mendelian randomization analysis was performed to assess the potential causality between NLR and AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NLR was associated with AD in the UK Biobank (HR: 1.03 per 1 SD, 95% CI: 1.01\u20131.05) but not in AoU (HR: 1.02, 95% CI: 0.92\u20131.14). A fixed effects model resulted in a pooled HR: 1.03 (95% CI: 1.02\u20131.05). These effects were robust to adjustment for C-reactive protein,\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 genotype status,\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b52 genotype status, and other AD risk factors. The MR analysis was performed with 214 NLR-associated variants but was not significant (IVW estimate: \u22120.001, p: 0.99).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Findings provide evidence for NLR as a biomarker for AD but not as a causal risk factor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251386813","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T18:52:55Z","timestamp":1761245575000},"page":"1302-1311","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between neutrophil to lymphocyte ratio and Alzheimer's disease in large biobank cohorts"],"prefix":"10.1177","volume":"108","author":[{"given":"Emily","family":"Drzymalla","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-8162","authenticated-orcid":false,"given":"Christy","family":"Avery","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Palta","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P","family":"Reiner","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-2803","authenticated-orcid":false,"given":"Quan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Center for Computational and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-193X","authenticated-orcid":false,"given":"Laura M","family":"Raffield","sequence":"additional","affiliation":[{"name":"Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2018.06.014"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01323-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.903455"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00812-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00757-x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016295"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-319148"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00754"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12568"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10265"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/1533317515602087"},{"key":"e_1_3_3_15_2","volume-title":"C-reactive protein: clinical relevance and interpretation. StatPearls","author":"Singh B","year":"2025","unstructured":"Singh B, Goyal A, Patel BC. C-reactive protein: clinical relevance and interpretation. StatPearls. Treasure Island, FL: StatPearls Publishing LLC., 2025."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1264383"},{"key":"e_1_3_3_17_2","first-page":"5","article-title":"Ratio of neutrophil to lymphocyte counts\u2013rapid and simple parameter of systemic inflammation and stress in critically ill","volume":"102","author":"Zahorec R","year":"2001","unstructured":"Zahorec R. Ratio of neutrophil to lymphocyte counts\u2013rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001; 102: 5\u201314.","journal-title":"Bratisl Lek Listy"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79431-7"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2703518"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.888946"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-00968-y"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1159\/000341583"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.05.005"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/psyg.12260"},{"key":"e_1_3_3_25_2","article-title":"Exploring the links among peripheral immunity, biomarkers, cognition, and neuroimaging in Alzheimer's disease","volume":"15","author":"Li JQ","year":"2023","unstructured":"Li JQ, Zhang YR, Wang HF, et al. Exploring the links among peripheral immunity, biomarkers, cognition, and neuroimaging in Alzheimer's disease. Alzheimers Dement (Amst) 2023; 15: e12517.","journal-title":"Alzheimers Dement (Amst)"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.773984"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01446-5"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-023-02683-0"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007679"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014399"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040501"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-021-00092-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjment-2023-300719"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.1042"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-021-02097-z"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-02053-5"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S206770"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1992.tb02015.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.9.1206"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dym276"},{"key":"e_1_3_3_43_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1056\/NEJMsr1809937","article-title":"The \u201cAll of Us\u201d Research program.","volume":"381","author":"Denny JC","year":"2019","unstructured":"Denny JC, Rutter JL, Goldstein DB, et al. The \u201cAll of Us\u201d Research program. N Engl J Med 2019; 381: 668\u2013676.","journal-title":"N Engl J Med"},{"key":"e_1_3_3_44_2","unstructured":"All of Us Research Program. Curated Data Repository (CDR) version 8 Release Notes https:\/\/support.researchallofus.org\/hc\/en-us\/articles\/30294451486356-Curated-Data-Repository-CDR-version-8-Release-Notes (accessed 25 April 2025)."},{"key":"e_1_3_3_45_2","volume-title":"Neutrophilia. StatPearls","author":"Tahir N","year":"2025","unstructured":"Tahir N, Zahra F. Neutrophilia. StatPearls. Treasure Island, FL: StatPearls Publishing LLC., 2025."},{"key":"e_1_3_3_46_2","unstructured":"National Heart Lung and Blood Institute. Lymphopenia: Diagnosis https:\/\/www.nhlbi.nih.gov\/health\/lymphopenia\/diagnosis (accessed July 3 2025)."},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201209"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000360"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-024-00444-0"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/jamia\/ocad260"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.008"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-021-00968-0"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac011"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2023.102782"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0305322"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-021-05507-5"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02281-6"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-70446-y"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-022-03579-2"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251386813","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877251386813","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251386813","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:24Z","timestamp":1777370964000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877251386813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":60,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1177\/13872877251386813"],"URL":"https:\/\/doi.org\/10.1177\/13872877251386813","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}