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28/100

✓ Peer-reviewed alzhub usefulness score 28 out of 100. Risk genes beyond APOE

Topic: Brain proteins, microglia and lab models

Alzheimer's disease (AD) affects over 55 million people worldwide and lacks effective disease-modifying therapies targeting neuroinflammation. Disease-associated microglia (DAM) are central effectors of AD neuroinflammation, yet cell-type-specific druggable kinase targets in human AD prefrontal cortex microglia have not been systematically identified at single-cell resolution. Here we apply a computational drug screening pipeline to the human prefrontal cortex snRNA-seq dataset GSE138852 (Mathys et al., Nature 2019) to identify SYK kinase as the top druggable target in microglial clusters of AD brain. ScVI dimensionality reduction and Leiden clustering of 13,096 high-quality nuclei from 6 AD and 6 control donors identified 7 cell populations; cluster 4 was confirmed as microglia by P2RY12 (0.992), CX3CR1 (0.666), CSF1R (0.816), and AIF1 (0.390) expression. Wilcoxon differential expression yielded 624 upregulated genes including SYK, CLEC7A, CD86, DOCK8, and SORL1. ChEMBL screening across 8 microglial DAM-relevant targets identified 6,230 NOVEL_ALL inhibitor candidates. Lead SYK inhibitors: CHEMBL3415598 (pChEMBL 11.00), fostamatinib (FDA-approved for ITP, pChEMBL 7.77), entospletinib (8.11), lanraplenib (8.21), mivavotinib (8.70). P2RY12 inhibitors: cangrelor (9.40) and ticagrelor (8.70), both FDA-approved. All confirmed NOVEL_ALL for the Alzheimer's disease / microglial indication. Patent pending. Pipeline: github.com/glenritschel/alzheimers-scrna.

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

APA 7th

Ritsachel, G. C., & Claude. (2026). Single-Cell Transcriptomic Identification of SYK Kinase as a Therapeutic Target in Disease-Associated Microglia for Alzheimer's Disease Treatment. Zenodo (CERN European Organization for Nuclear Research). https://doi.org/10.5281/zenodo.19194338

Vancouver

Ritsachel GC, Claude. Single-Cell Transcriptomic Identification of SYK Kinase as a Therapeutic Target in Disease-Associated Microglia for Alzheimer's Disease Treatment. Zenodo (CERN European Organization for Nuclear Research). 2026. doi:10.5281/zenodo.19194338.

BibTeX

@article{ritsachel2026-31d8a212,
  author  = {Ritsachel, Glen Charles and Claude},
  title   = {{Single-Cell Transcriptomic Identification of SYK Kinase as a Therapeutic Target in Disease-Associated Microglia for Alzheimer's Disease Treatment}},
  journal = {Zenodo (CERN European Organization for Nuclear Research)},
  year    = {2026},
  doi     = {10.5281/zenodo.19194338},
  url     = {https://doi.org/10.5281/zenodo.19194338}
}

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.

Key findings

ChEMBL screening across 8 microglial DAM-relevant targets identified 6,230 NOVEL_ALL inhibitor candidates.
Lead SYK inhibitors: CHEMBL3415598 (pChEMBL 11.00), fostamatinib (FDA-approved for ITP, pChEMBL 7.77), entospletinib (8.11), lanraplenib (8.21), mivavotinib (8.70).
P2RY12 inhibitors: cangrelor (9.40) and ticagrelor (8.70), both FDA-approved.
All confirmed NOVEL_ALL for the Alzheimer's disease / microglial indication.
Pipeline: github.com/glenritschel/alzheimers-scrna.

Why it matters

This is a computational analysis of existing human brain data that identifies SYK kinase as a possible drug target and lists candidate inhibitors, so it does not test any treatment in patients. No clinical benefit, cure or prevention is shown.

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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, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record and senior author's track record, so those were left out: it earned 26 of the 92 points we could judge it on, which is 28 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Zenodo (CERN European Organization for Nuclear Research))
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
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	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	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	— / 4	Senior author's record not available — left out of this score
Institution's track record	0 / 3	Anthropic (United States): institution h-index 49 (OpenAlex)
Multi-centre collaboration	0 / 3	OpenAlex lists 1 institution(s) in 0 countries — 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
Points	26 / 92	Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 26 of the 92 points we could judge it on is 28 out of 100.
Total	28 / 100	—

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