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A wealth of clinical studies support that the disease starts to develop decades before the first symptoms appear, emphasizing the importance of studying early changes for improving early diagnosis and guiding toward novel treatment strategies. Protein glycosylation is altered in AD but it remains to be clarified why these alterations occur and how they affect the disease development. Here, we used a glycomics approach to search for alterations in protein glycosylation in cerebrospinal fluid (CSF) in AD compared with nondemented controls. Using both matrix\u2010assisted laser desorption ionization\u2010time of flight and liquid chromatography\u2013electrospray mass spectrometry, we observed an increase in N\u2010glycans carrying bisecting N\u2010acetylglucosamine in AD. Based on those findings, we designed an enzyme\u2010linked multiwell plate assay to quantify N\u2010glycans binding to the lectin <jats:italic>Phaseolus\u00a0vulgaris<\/jats:italic> Erythroagglutinin (PHA\u2010E), which is specific for N\u2010glycans containing bisecting N\u2010acetylglucosamine. Using this assay, we found a similar increase in CSF in AD compared with controls. Further analysis of CSF from 242 patients with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or AD dementia revealed significantly increased binding to PHA\u2010E in MCI and AD compared to SCI. Interestingly, PHA\u2010E binding correlated with CSF levels of phosphorylated tau and total tau and this correlation was most prominent in the SCI group (<jats:italic>R<\/jats:italic>\u00a0=\u00a00.53\u20130.54). This study supports a link between N\u2010glycosylation, neurodegeneration, and tau pathology in AD and suggests that glycan biomarkers have potential to identify SCI cases at risk of developing AD.<\/jats:p>","DOI":"10.1111\/febs.15197","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T04:21:11Z","timestamp":1577766071000},"page":"3221-3234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Glycan biomarkers for Alzheimer disease correlate with T\u2010tau and P\u2010tau in cerebrospinal fluid in subjective cognitive impairment"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2143-7052","authenticated-orcid":false,"given":"Sophia","family":"Schedin\u2010Weiss","sequence":"first","affiliation":[{"name":"Division of Neurogeriatrics Center for Alzheimer Research Department of Neurobiology, Care Sciences, and Society Karolinska Institutet Solna 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