{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:06Z","timestamp":1792790406854,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Neuroscience","reference-count":27,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"NINDS","award":["NS141137"],"award-info":[{"award-number":["NS141137"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIA","award":["AG075798"],"award-info":[{"award-number":["AG075798"]}]},{"name":"NIA","award":["AG082193"],"award-info":[{"award-number":["AG082193"]}]},{"name":"Alzheimer's Association","award":["AARG&#8208;22&#8208;974437"],"award-info":[{"award-number":["AARG&#8208;22&#8208;974437"]}],"id":[{"id":"https:\/\/ror.org\/0375f4d26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Florida Department of Health","award":["23A12"],"award-info":[{"award-number":["23A12"]}],"id":[{"id":"https:\/\/ror.org\/03e1xkn26","id-type":"ROR","asserted-by":"crossref"}]},{"award":["American Student Scholarships in Cardiovascular Disease and Stroke"],"award-info":[{"award-number":["American Student Scholarships in Cardiovascular Disease and Stroke"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Florida Education Fund","award":["McKnight Doctoral Fellowship"],"award-info":[{"award-number":["McKnight Doctoral Fellowship"]}],"id":[{"id":"https:\/\/ror.org\/03d6fb891","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Dysregulation of the immune system is increasingly recognized as a contributor to Alzheimers disease (AD) progression, partly through neutrophil adhesion to the cerebral vasculature, which promotes hypoperfusion in AD. Because sialic acid (SA) residues on membrane glycoproteins regulate neutrophil\u2013endothelial interactions, we investigated whether neutrophil sialylation is altered in AD and whether reducing it improves cerebral vascular function.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Approach and Results<\/jats:title>\n                  <jats:p>Lectin blots of isolated neutrophils showed increased SA levels in two AD mouse models, 5xFAD and APP-SAA. We identified \u03b12,3 sialyltransferase-IN-1 as a small-molecule inhibitor that reduces sialylation in vivo. Treating 5xFAD mice with this inhibitor decreased SA on neutrophil membranes, increased cerebral blood flow, and reduced capillary stalling. Leukocytes from patients with preclinical AD and mild cognitive impairment also had higher SA levels than those from age-matched healthy controls.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Elevated terminal sialylation of neutrophil glycoproteins contributes to capillary stalling and cerebral hypoperfusion in AD. Neutrophil sialylation may serve as both a biomarker and a therapeutic target for improving cerebral blood flow and slowing disease progression.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.23.753660","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:35:21Z","timestamp":1790289321000},"source":"Crossref","is-referenced-by-count":0,"title":["Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer\u2019s Models"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1626-8866","authenticated-orcid":false,"given":"Nairuti Nikhil","family":"Bhatt","sequence":"first","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"University of South Alabama, Frederick College of Medicine, Department of Physiology and Cell Biology, Mobile, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynab","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"Department of Physiology and Neuroscience, Epstein Family Alzheimer\u2019s Therapeutic Research Institute Keck School of Medicine of the University of Southern California, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolie","family":"Janulis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"Department of Physiology and Neuroscience, Epstein Family Alzheimer\u2019s Therapeutic Research Institute Keck School of Medicine of the University of Southern California, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"Department of Physiology and Neuroscience, Epstein Family Alzheimer\u2019s Therapeutic Research Institute Keck School of Medicine of the University of Southern California, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Weick","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience, Epstein Family Alzheimer\u2019s Therapeutic Research Institute Keck School of Medicine of the University of Southern California, San Diego, CA, USA"},{"name":"Biochemistry & Molecular Biology Graduate Program, Miller School of Medicine at the University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia Andrea","family":"Franciosa","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Rodriguez Moore","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"Department of Physiology and Neuroscience, Epstein Family Alzheimer\u2019s Therapeutic Research Institute Keck School of Medicine of the University of Southern California, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Agatemor","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"Department of Chemistry, University of Miami, Miami, USA"},{"name":"Department of Chemistry, Bucknell University, Lewisburg, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Galvin","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Brain Health, Department of Neurology, University of Miami Miller School of Medicine, Boca Raton, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9414-6590","authenticated-orcid":false,"given":"Oliver","family":"Bracko","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami, Miami, USA"},{"name":"Department of Physiology and Neuroscience, Epstein Family Alzheimer\u2019s Therapeutic Research Institute Keck School of Medicine of the University of Southern California, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"2","key":"2026092803500867000_2026.09.23.753660v1.1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.trci.2016.05.001","article-title":"The roles of inflammation and immune mechanisms in Alzheimers disease","volume":"2","year":"2016","journal-title":"Alzheimers Dement (N Y)"},{"key":"2026092803500867000_2026.09.23.753660v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01155-w"},{"key":"2026092803500867000_2026.09.23.753660v1.3","doi-asserted-by":"crossref","unstructured":"Anwer M , Poliakova T , Albanus RD , Bhuiyan MIH , Brickman AM , Chaudhuri S , et al. 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