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Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification
Zhang C, Fang D, Zhang L.. Drug design, development and therapy, 2026-06-26
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) pathogenesis is increasingly recognized as involving blood-brain barrier (BBB) and neurovascular unit (NVU) destabilization. The brain endothelial glycocalyx-a blood-facing glycan-rich interface-represents a critical but under-characterized determinant of BBB dysfunction in AD. In this review, we systematically reappraised glycocalyx abnormality mechanisms, distinguishing robust causal evidence from murine models from limited human observational data. We propose a four-dimensional interface-state framework (structural, glycosylation, transport, inflammatory) to stratify patients beyond binary "leaky versus intact" classifications. Glycocalyx deterioration in AD reflects compartmentalized remodeling (early mucin-domain depletion) rather than uniform shedding. A reversible therapeutic window exists in APOE4 carriers and mild cognitive impairment, but collapses with concurrent cerebral amyloid angiopathy (CAA) or amyloid-related imaging abnormalities (ARIA). Pathological glycocalyx disruption amplifies nonproductive vascular retention rather than parenchymal penetration. We advocate a hierarchical "repair-first, transport-engineering-second, exploitation-last" strategy. This repositions the glycocalyx as a decisive arbiter governing BBB-targeted interventions in AD, not merely a structural appendage.
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APA 7th
Zhang, C., Fang, D., & Zhang, L. (2026). Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification. Drug design, development and therapy. https://doi.org/10.2147/dddt.s619901
Vancouver
Zhang C, Fang D, Zhang L. Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification. Drug design, development and therapy. 2026. doi:10.2147/dddt.s619901. PMID: 42381975.
BibTeX
@article{zhang2026-42381975,
author = {Zhang, C. and Fang, D. and Zhang, L.},
title = {{Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification}},
journal = {Drug design, development and therapy},
year = {2026},
doi = {10.2147/dddt.s619901},
pmid = {42381975},
url = {https://doi.org/10.2147/dddt.s619901}
}
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Key findings
- We propose a four-dimensional interface-state framework (structural, glycosylation, transport, inflammatory) to stratify patients beyond binary "leaky versus intact" classifications.
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Study details
- Evidence strengthLow
How this study scored 47/100
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, 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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Drug design, development and therapy) |
| 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 | — / 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 | 2 / 2 | Indexed in PubMed (PMID 42381975) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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