Evidence map›Paper›PMID 42265388›Full record

ArticleNature metabolism2026

Hyperglycosylation is a metabolic driver of Alzheimer's disease.

Tara R Hawkinson, Zizhen Liu, Roberto A Ribas, Terrymar Medina, Rikke S Nielsen, Harrison A Clarke, Xin Ma, Angela C Mueller, Adrielle F Plasencia, Alexander L Sheer and 29 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Tara R Hawkinson *Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-8743-5503
Zizhen Liu *Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Roberto A RibasDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0009-0008-9024-1292
Terrymar MedinaDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Rikke S NielsenDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Harrison A ClarkeDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Xin MaDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0009-0009-3347-4257
Angela C MuellerDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Adrielle F PlasenciaDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Alexander L SheerDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Samantha T SimpsonDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Charles M SotoDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Jessica SudderthChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Feng CaiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5192-9520
Alex R CantrellDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0003-4134-9981
Matthieu G ColpaertDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Cameron J ShedlockDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Lei WuDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-1474-8082
Lyndsay E A YoungPharmacology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Damon D KooserDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Li ChenCenter for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0001-9372-5606
Alison M RyanDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0009-0009-7307-053X
Sadi QuinonesDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Jihye SonDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Parastoo AzadiComplex Carbohydrate Research Center, University of Georgia-Athens, Athens, GA, USA.
Ralph J DeberardinisChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-2705-7432
Stefan ProkopCenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, USA.
Derek AllisonDepartment of Pathology and Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0002-5119-2474
Shuang YangHealth Outcome and Biomedical Informatics, University of Florida, Gainesville, FL, USA.
Hongyu ChenHealth Outcome and Biomedical Informatics, University of Florida, Gainesville, FL, USA.
Yu HuangRegenstrief Institute, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0001-7373-4716
Xing HeRegenstrief Institute, Indianapolis, IN, USA.
Kimberly M AlongeCenter for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-2171-1640
Jingchuan GuoRegenstrief Institute, Indianapolis, IN, USA.
Yi GuoHealth Outcome and Biomedical Informatics, University of Florida, Gainesville, FL, USA.
Jiang BianRegenstrief Institute, Indianapolis, IN, USA.
Craig W Vander KooiDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Matthew S GentryDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0001-5253-9049
Ramon C SunDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA. ramonsun@ufl.edu.ORCID http://orcid.org/0000-0002-3009-1850

Funding

Brain Glycogen-Metabolism,Mechanisms, and Therapeutic PotentialR35NS116824 · NINDS · UNIVERSITY OF FLORIDA · 2024 to 2025
$3.6M
NINDS NIH HHS R35 NS116824
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder marked by progressive cognitive decline. Metabolic disruptions are widely observed, yet their involvement in the molecular aetiology of AD remains underexplored. Here we identify hyperglycosylation as a driver of AD. Integrating spatial metabolomics, lipidomics and glycomics in transgenic AD mouse models and post-mortem human AD samples, along with advanced spatial isotopic tracing pulse-chase analysis of N-linked glycans, we demonstrate that the conserved phenotype of brain hyperglycosylation is driven by increased glycan biosynthesis. Genetic knockdown of glycan biosynthetic enzymes improves cognitive outcomes in AD mice whereas oral glucosamine supplementation impairs them. A retrospective analysis of electronic health records from patients with AD with varying disease severity shows that glucosamine supplementation is associated with accelerated AD progression and worsened survival. Overall, these results establish hyperglycosylation as a pathological driver of AD and highlight glycan metabolism as an actionable target in the fight against AD.

Indexed as

Alzheimer DiseaseAnimalsBrainDisease Models, AnimalGlucosamineGlycomicsGlycosylationHumansMetabolomicsMiceMice, TransgenicPolysaccharidesGlucosaminePolysaccharides

Identifiers

PMID42265388
PMCPMC13303091

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.