A glycan epitope correlates with tau in serum and predicts progression to Alzheimer's disease in combination with APOE4 allele status

Alzheimers Dement. 2023 Jul;19(7):3244-3249. doi: 10.1002/alz.13024. Epub 2023 Apr 12.

Abstract

Introduction: There is an urgent need for novel blood biomarkers for the detection of Alzheimer's disease (AD). We previously showed that levels of the bisecting N-acetylglucosamine glycan epitope was elevated in cerebrospinal fluid in AD. However, its diagnostic value in blood is unknown.

Methods: We analyzed blood levels of bisecting N-acetylglucosamine and total tau in a retrospective cohort of 233 individuals. Progression to AD was compared between the groups using Cox regression. The predictive value of the biomarkers was determined by logistic regression.

Results: Bisecting N-acetylglucosamine correlated with tau levels (p < 0.0001). Individuals with an intermediate tau/bisecting N-acetylglucosamine ratio had elevated AD risk (hazard ratio = 2.06, 95% confidence interval [CI]: 1.18-3.6). Moreover, a combined model including tau/bisecting N-acetylglucosamine ratio, apolipoprotein E (APOE) ε4 status, and Mini-Mental State Examination score predicted future AD (area under the curve = 0.81, 95% CI: 0.68-0.93).

Discussion: Bisecting N-acetylglucosamine in combination with tau is a valuable blood biomarker for predicting AD.

Keywords: APOE; Alzheimer's disease; N-glycosylation; biomarkers; blood; dementia; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine
  • Alleles
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / diagnosis
  • Genotype
  • Humans
  • Peptide Fragments / cerebrospinal fluid
  • Retrospective Studies
  • tau Proteins / cerebrospinal fluid

Substances

  • Apolipoprotein E4
  • tau Proteins
  • Acetylglucosamine
  • Biomarkers
  • Peptide Fragments
  • Amyloid beta-Peptides