A glycan epitope correlates with tau in serum and predicts progression to Alzheimer's disease in combination with APOE4 allele status.
Humans
Alzheimer Disease
/ diagnosis
Apolipoprotein E4
/ genetics
tau Proteins
/ cerebrospinal fluid
Retrospective Studies
Alleles
Acetylglucosamine
Genotype
Biomarkers
/ cerebrospinal fluid
Peptide Fragments
/ cerebrospinal fluid
Amyloid beta-Peptides
/ cerebrospinal fluid
Cognitive Dysfunction
/ diagnosis
APOE
Alzheimer's disease
N-glycosylation
biomarkers
blood
dementia
tau
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
19
01
2023
received:
21
11
2022
accepted:
20
01
2023
medline:
27
7
2023
pubmed:
13
4
2023
entrez:
12
4
2023
Statut:
ppublish
Résumé
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. 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. 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). Bisecting N-acetylglucosamine in combination with tau is a valuable blood biomarker for predicting AD.
Substances chimiques
Apolipoprotein E4
0
tau Proteins
0
Acetylglucosamine
V956696549
Biomarkers
0
Peptide Fragments
0
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3244-3249Informations de copyright
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Karran E, Mercken M, de Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011;10:698-712.
Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19:422-433.
Palmqvist S, Stomrud E, Cullen N, et al. An accurate fully automated panel of plasma biomarkers for Alzheimer's disease. Alzheimer's & Dementia. 2023;19:1204-1215.
Gaunitz S, Tjernberg LO, Schedin-Weiss S. What can N-glycomics and N-glycoproteomics of cerebrospinal fluid tell us about Alzheimer disease? Biomolecules. 2021;11:858.
Kizuka Y, Kitazume S, Fujinawa R, et al. An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer's disease. EMBO Mol Med. 2015;7:175-189.
Chen Q, Tan Z, Guan F, Ren Y. The essential functions and detection of bisecting GlcNAc in cell biology. Front Chem. 2020;8:511.
Sato Y, Naito Y, Grundke-Iqbal I, Iqbal K, Endo T. Analysis of N -glycans of pathological tau: possible occurrence of aberrant processing of tau in Alzheimer's disease. FEBS Lett. 2001;496:152-160.
Nagae M, Kanagawa M, Morita-Matsumoto K, et al. Atomic visualization of a flipped-back conformation of bisected glycans bound to specific lectins. Sci Rep. 2016;6:22973.
Schedin-Weiss S, Gaunitz S, Sui P, et al. Glycan biomarkers for Alzheimer disease correlate with T-tau and P-tau in cerebrospinal fluid in subjective cognitive impairment. FEBS J. 2020;287:3221-3234.
Lagergren M, Fratiglioni L, Hallberg IR, et al. A longitudinal study integrating population, care and social services data. The Swedish National Study on Aging and Care (SNAC). Aging Clin Exp Res. 2004;16:158-168.
Xia X, Wang R, Vetrano DL, et al. From normal cognition to cognitive impairment and Dementia: impact of orthostatic hypotension. Hypertension. 2021;78:769-778.
Cho BG, Veillon L, Mechref Y. N-Glycan profile of cerebrospinal fluids from Alzheimer's disease patients using liquid chromatography with mass spectrometry. J Proteome Res. 2019;18:3770-3779.
Gizaw ST, Ohashi T, Tanaka M, Hinou H, Nishimura S-I. Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery. Biochim Biophys Acta Gen Subj. 2016;1860:1716-1727.
Palmigiano A, Barone R, Sturiale L, et al. CSF N-glycoproteomics for early diagnosis in Alzheimer's disease. J Proteomics. 2016;131:29-37.
Jack CR, Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron. 2013;80:1347-1358.
Wang J-Z, Grundke-Iqbal I, Iqbal K. Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer's disease. Nat Med. 1996;2:871-875.
Thijssen EH, la Joie R, Strom A, et al. Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study. Lancet Neurol. 2021;20:739-752.
Palmqvist S, Tideman P, Cullen N, et al. Prediction of future Alzheimer's disease dementia using plasma phospho-tau combined with other accessible measures. Nat Med. 2021;27:1034-1042.
Losev Y, Frenkel-Pinter M, Abu-Hussien M, et al. Differential effects of putative N-glycosylation sites in human tau on Alzheimer's disease-related neurodegeneration. Cellular and Molecular Life Sciences. 2021;78:2231-2245.