Bisecting N-Acetylglucosamine Correlates with Phospho-Tau181 in Subjective Cognitive Decline but not in Control Cases

Article type: Research Article

Authors: Egebäck Arulf, Sofia^a | Ziyue Zhou, Robin^a | Kirsebom, Bjørn-Eivind^{b; c; d; e} | Jejcic, Alenka^a | Fladby, Tormod^{d; e} | Winblad, Bengt^{a; f; *} | Tjernberg, Lars^{a; *} | Schedin-Weiss, Sophia^{a; *}

Affiliations: [a] Department of Neurobiology, Division of Neurogeriatrics, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Solna, Sweden | [b] Department of Neurology, University Hospital of North Norway, Troms–, Norway | [c] Department of Psychology, Faculty of Health Sciences, The Arctic University of Norway, Troms–, Norway | [d] Department of Neurology, Akershus University Hospital, L–renskog, Norway | [e] Institute of Clinical Medicine, University of Oslo, Oslo, Norway | [f] Theme Inflammation and Aging, Karolinska University Hospital, Huddinge, Sweden

Correspondence: [*] Correspondence to: Bengt Winblad, Lars Tjernberg, and Sophia Schedin Weiss, Department of Neurobiology, Division of Neurogeriatrics, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, BioClinicum, J9:20, Visionsgatan 4, 171 64 Solna, Sweden. E-mails: bengt.winblad@ki.se; lars.tjernberg@ki.se; sophia.schedin.weiss@ki.se.

Abstract: Background:The N-glycan structure bisecting N-acetylglucosamine (bisecting GlcNAc) is present on several N-glycans that are elevated in Alzheimer’s disease (AD), and previous studies have shown that bisecting GlcNAc levels correlate with total tau and phospho-tau181 in cerebrospinal fluid at early stages of AD. A recent population-based study showed that bisecting GlcNAc correlates with total tau also in blood and that this correlation could predict conversion to dementia. Objective:In this study, we have further investigated how bisecting GlcNAc relates to total tau and phospho-tau 181 in cerebrospinal fluid samples from controls and cases with early cognitive deficits, stratified by amyloid/tau status and gender. Methods:Relative levels of bisecting GlcNAc in cerebrospinal fluid were measured by an enzyme-linked lectin assay in individuals with subjective cognitive decline, mild cognitive impairment and controls from the Norwegian Dementia Disease Initiation cohort. Results:As in our previous study, the correlation between bisecting GlcNAc and total tau or phospho-tau181 was particularly strong in the subjective cognitive decline group. The correlation was observed in amyloid negative and tau negative as well as amyloid positive and tau positive individuals, both in females and in males. Interestingly, among the amyloid negative and tau negative individuals, the correlation was observed in individuals with subjective cognitive decline but not in the controls. Conclusions:Thus, bisecting GlcNAc could be a biomarker for early cognitive decline.

Keywords: Alzheimer’s disease, bisecting N-acetylglucosamine, dementia, mild cognitive impairment, N-glycosylation, phospho-tau, subjective cognitive decline, total tau

DOI: 10.3233/JAD-240628

Journal: Journal of Alzheimer's Disease, vol. 100, no. s1, pp. S93-S101, 2024