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Advanced Glycation End Products Induce Microglial Activation and Impair Neurodevelopment in Human iPSC-Derived Brain Organoids
Rika Kumar, Grace Shinn, Jimmy Lin, Qingshun Quinn Li, Yiling Hong. Organoids, 2026-04-20
Topic: Brain proteins, microglia and lab models
Advanced Glycation End Products (AGEs) are reactive compounds formed through the non-enzymatic glycation of proteins, lipids, or nucleic acids due to exposure to reducing sugars. They accumulate through endogenous metabolic dysregulation and exogenous dietary intake, particularly high-fat and high-sugar foods prepared at high temperatures. The interaction between AGEs and their receptor, RAGE (receptor for Advanced Glycation End Products), has been implicated in a range of pathological conditions, including diabetes and metabolic syndrome. However, the impact of AGEs accumulation on neurodevelopment remains poorly understood. In this study, we investigated the effects of AGEs on human-induced pluripotent stem cell (iPSC)-derived cerebral organoids comprising neurons, astrocytes, and microglia. Our findings reveal that AGEs induce RAGE expression, leading to microglial activation, increased deposition of amyloid-beta (Aβ) aggregates, and impaired neurodevelopment. Additionally, elevated levels of AGE-modified proteins, along with altered microglial polarization, were observed in cerebral organoids modeling Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism–Dementia Complex (ALS-PDC). These findings demonstrate AGEs as active drivers of neurodevelopmental disruption and establish a mechanistic link between metabolic stress and increased susceptibility to neurodegenerative disease.
Key findings
- Our findings reveal that AGEs induce RAGE expression, leading to microglial activation, increased deposition of amyloid-beta (Aβ) aggregates, and impaired neurodevelopment.
- These findings demonstrate AGEs as active drivers of neurodevelopmental disruption and establish a mechanistic link between metabolic stress and increased susceptibility to neurodegenerative disease.
Why it matters
In human iPSC-derived brain organoids, advanced glycation end-products activated microglia, increased amyloid-beta aggregates, and impaired neurodevelopment. These are laboratory findings in a model system, so they do not yet show any way to treat, cure, or prevent Alzheimer's disease in people.
Study details
- Evidence strengthLow
How this study scored 28/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Organoids) |
| Journal's citation record | 0 / 4 | Organoids: journal h-index 13 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | Laboratory or animal study (title names “ipsc”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Yiling Hong: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Western University of Health Sciences: institution h-index 183 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Total | 28 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Kumar, R., Shinn, G., Lin, J., Li, Q. Q., & Hong, Y. (2026). Advanced Glycation End Products Induce Microglial Activation and Impair Neurodevelopment in Human iPSC-Derived Brain Organoids. Organoids. https://doi.org/10.3390/organoids5020012
Vancouver
Kumar R, Shinn G, Lin J, Li QQ, Hong Y. Advanced Glycation End Products Induce Microglial Activation and Impair Neurodevelopment in Human iPSC-Derived Brain Organoids. Organoids. 2026. doi:10.3390/organoids5020012.
BibTeX
@article{kumar2026-781836ef,
author = {Kumar, Rika and Shinn, Grace and Lin, Jimmy and Li, Qingshun Quinn and Hong, Yiling},
title = {{Advanced Glycation End Products Induce Microglial Activation and Impair Neurodevelopment in Human iPSC-Derived Brain Organoids}},
journal = {Organoids},
year = {2026},
doi = {10.3390/organoids5020012},
url = {https://doi.org/10.3390/organoids5020012}
}
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