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50/100

✓ Peer-reviewed alzhub usefulness score 50 out of 100. Mild cognitive impairment

Topic: Brain proteins, microglia and lab models

Plain-language summary

Alzheimer disease (AD) is a growing problem for aging populations worldwide. Despite significant efforts, no therapeutics are available that stop or slow progression of AD, which has driven interest in the basic causes of AD and the search for new therapeutic strategies. Longitudinal studies have clarified that defects in glucose metabolism occur in patients exhibiting Mild Cognitive Impairment (MCI) and glucose hypometabolism is an early pathological change within AD brain. Further, type 2 diabetes mellitus (T2DM) is a strong risk factor for the development of AD. These findings have stimulated interest in the possibility that disrupted glucose regulated signaling within the brain could contribute to the progression of AD. One such process of interest is the addition of O-linked N-acetylglucosamine (O-GlcNAc) residues onto nuclear and cytoplasmic proteins within mammals. O-GlcNAc is notably abundant within brain and is present on hundreds of proteins including several, such as tau and the amyloid precursor protein, which are involved in the pathophysiology AD. The cellular levels of O-GlcNAc are coupled to nutrient availability through the action of just two enzymes. O-GlcNAc transferase (OGT) is the glycosyltransferase that acts to install O-GlcNAc onto proteins and O-GlcNAcase (OGA) is the glycoside hydrolase that acts to remove O-GlcNAc from proteins. Uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) is the donor sugar substrate for OGT and its levels vary with cellular glucose availability because it is generated from glucose through the hexosamine biosynthetic pathway (HBSP). Within the brains of AD patients O-GlcNAc levels have been found to be decreased and aggregates of tau appear to lack O-GlcNAc entirely. Accordingly, glucose hypometabolism within the brain may result in disruption of the normal functions of O-GlcNAc within the brain and thereby contribute to downstream neurodegeneration. While this hypothesis remains largely speculative, recent studies using different mouse models of AD have demonstrated the protective benefit of pharmacologically increased brain O-GlcNAc levels. In this review we summarize the state of knowledge in the area of O-GlcNAc as it pertains to AD while also addressing some of the basic biochemical roles of O-GlcNAc and how these might contribute to protecting against AD and other neurodegenerative diseases.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Yuzwa, S. A., & Vocadlo, D. J. (2014). O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond. Chemical Society reviews. https://doi.org/10.1039/c4cs00038b

Vancouver

Yuzwa SA, Vocadlo DJ. O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond. Chemical Society reviews. 2014. doi:10.1039/c4cs00038b. PMID: 24759912.

BibTeX

@article{yuzwa2014-24759912,
  author  = {Yuzwa, S. A. and Vocadlo, D. J.},
  title   = {{O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond}},
  journal = {Chemical Society reviews},
  year    = {2014},
  doi     = {10.1039/c4cs00038b},
  pmid    = {24759912},
  url     = {https://doi.org/10.1039/c4cs00038b}
}

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How to read this study

Design: this is a follow-up (cohort) study. People are observed over time and not assigned to anything, so an association can reflect other differences between groups. Look at how long follow-up lasted, how many dropped out, and whether the authors adjusted for age, education and other health conditions.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded moderate. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Moderate means the abstract mentions a cohort, case-control or longitudinal design. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Despite significant efforts, no therapeutics are available that stop or slow progression of AD, which has driven interest in the basic causes of AD and the search for new therapeutic strategies.
These findings have stimulated interest in the possibility that disrupted glucose regulated signaling within the brain could contribute to the progression of AD.
Accordingly, glucose hypometabolism within the brain may result in disruption of the normal functions of O-GlcNAc within the brain and thereby contribute to downstream neurodegeneration.
While this hypothesis remains largely speculative, recent studies using different mouse models of AD have demonstrated the protective benefit of pharmacologically increased brain O-GlcNAc levels.

Why it matters

This review links disrupted glucose metabolism and the O-GlcNAc process to Alzheimer's disease and notes that no treatments currently stop or slow it. It discusses possible targets for future therapy but reports no tested treatment or cure.

Study details

Study designlongitudinal study
Evidence strengthModerate

How this study scored 50/100

Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Chemical Society reviews)
Journal's citation record	4 / 4	Chemical Society Reviews: journal h-index 762 (OpenAlex, 2026-10-29)
Study design	7 / 12	A longitudinal study following the same people over time
Strength of evidence	3 / 5	Rated “moderate” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	2014 — within 20 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	5 / 7	Cited 248 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	17.7 citations a year over 14 year(s) since 2014
Impact for its field and year	2 / 6	Cited 1.4× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 2 other studies in this library
Still being cited	2 / 4	Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author David J. Vocadlo: h-index 67 (OpenAlex, whole career)
Institution's track record	0 / 3	Simon Fraser University: institution h-index 657 (OpenAlex)
Multicenter collaboration	0 / 3	OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete)
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 24759912)
Free to read	0 / 2	Behind a paywall — scores zero
Total	50 / 100	—

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