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Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models
Bhatt NN, Tabrizi Z, Janulis J, Chakraborty S, Weick M, Franciosa SA, Rodriguez Moore G, Agatemor C et al.. bioRxiv, 2026-09-24
Topic: Inflammation, microglia and astrocytes
Objective Dysregulation of the immune system is increasingly recognized as a contributor to Alzheimers disease (AD) progression, partly through neutrophil adhesion to the cerebral vasculature, which promotes hypoperfusion in AD. Because sialic acid (SA) residues on membrane glycoproteins regulate neutrophil–endothelial interactions, we investigated whether neutrophil sialylation is altered in AD and whether reducing it improves cerebral vascular function. Approach and Results Lectin blots of isolated neutrophils showed increased SA levels in two AD mouse models, 5xFAD and APP-SAA. We identified α2,3 sialyltransferase-IN-1 as a small-molecule inhibitor that reduces sialylation in vivo. Treating 5xFAD mice with this inhibitor decreased SA on neutrophil membranes, increased cerebral blood flow, and reduced capillary stalling. Leukocytes from patients with preclinical AD and mild cognitive impairment also had higher SA levels than those from age-matched healthy controls. Conclusions Elevated terminal sialylation of neutrophil glycoproteins contributes to capillary stalling and cerebral hypoperfusion in AD. Neutrophil sialylation may serve as both a biomarker and a therapeutic target for improving cerebral blood flow and slowing disease progression.
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APA 7th
Bhatt, N. N., Tabrizi, Z., Janulis, J., Chakraborty, S., Weick, M., Franciosa, S. A., et al. (2026). Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models. bioRxiv. https://doi.org/10.64898/2026.09.23.753660
Vancouver
Bhatt NN, Tabrizi Z, Janulis J, Chakraborty S, Weick M, Franciosa SA, et al. Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models. bioRxiv. 2026. doi:10.64898/2026.09.23.753660.
BibTeX
@article{bhatt2026-94d50e55,
author = {Bhatt, N. N. and Tabrizi, Z. and Janulis, J. and Chakraborty, S. and Weick, M. and Franciosa, S. A. and Rodriguez Moore, G. and Agatemor, C. and others},
title = {{Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.23.753660},
url = {https://doi.org/10.64898/2026.09.23.753660}
}
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Key findings
- Approach and Results Lectin blots of isolated neutrophils showed increased SA levels in two AD mouse models, 5xFAD and APP-SAA.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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