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Molecular subtyping of Alzheimer's disease using RNA sequencing data reveals novel mechanisms and targets
Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Wang E, Horgusluoglu-Moloch E et al.. Science advances, 2021-01-06
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD), the most common form of dementia, is recognized as a heterogeneous disease with diverse pathophysiologic mechanisms. In this study, we interrogate the molecular heterogeneity of AD by analyzing 1543 transcriptomes across five brain regions in two AD cohorts using an integrative network approach. We identify three major molecular subtypes of AD corresponding to different combinations of multiple dysregulated pathways, such as susceptibility to tau-mediated neurodegeneration, amyloid-β neuroinflammation, synaptic signaling, immune activity, mitochondria organization, and myelination.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Neff, R. A., Wang, M., Vatansever, S., Guo, L., Ming, C., Wang, Q., et al. (2021). Molecular subtyping of Alzheimer's disease using RNA sequencing data reveals novel mechanisms and targets. Science advances. https://doi.org/10.1126/sciadv.abb5398
Vancouver
Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, et al. Molecular subtyping of Alzheimer's disease using RNA sequencing data reveals novel mechanisms and targets. Science advances. 2021. doi:10.1126/sciadv.abb5398. PMID: 33523961.
BibTeX
@article{neff2021-33523961,
author = {Neff, R. A. and Wang, M. and Vatansever, S. and Guo, L. and Ming, C. and Wang, Q. and Wang, E. and Horgusluoglu-Moloch, E. and others},
title = {{Molecular subtyping of Alzheimer's disease using RNA sequencing data reveals novel mechanisms and targets}},
journal = {Science advances},
year = {2021},
doi = {10.1126/sciadv.abb5398},
pmid = {33523961},
url = {https://doi.org/10.1126/sciadv.abb5398}
}
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Key findings
- In this study, we interrogate the molecular heterogeneity of AD by analyzing 1543 transcriptomes across five brain regions in two AD cohorts using an integrative network approach.
- We identify three major molecular subtypes of AD corresponding to different combinations of multiple dysregulated pathways, such as susceptibility to tau-mediated neurodegeneration, amyloid-β neuroinflammation, synaptic signaling, immune activity, mitochondria organization, and myelination.
- Multiscale network analysis reveals subtype-specific drivers such as GABRB2 , LRP10 , MSN , PLP1 , and ATP6V1A We further demonstrate that variations between existing AD mouse models recapitulate a certain degree of subtype heterogeneity, which may partially explain why a vast majority of drugs that succeeded in specific mouse models do not align with generalized human trials across all AD subtypes.
- Therefore, subtyping patients with AD is a critical step toward precision medicine for this devastating disease.
Why it matters
By analyzing 1543 transcriptomes from two Alzheimer's disease cohorts, this study identified three molecular subtypes of the disease involving different dysregulated pathways. It describes disease heterogeneity and does not test or establish any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science advances) |
| Journal's citation record | 3 / 4 | Science Advances: journal h-index 378 (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 | 3 / 5 | 2021 — within 6 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 305 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 43.6 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 28.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 3 / 4 | Cited 175 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Bin Zhang: h-index 96 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Icahn School of Medicine at Mount Sinai: institution h-index 1,331 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33523961) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
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