Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.
C, Z., D, F., & L, Z. (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
C Z, D F, L Z. 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
C Z, D F, L Z. Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.[J]. Drug design, development and therapy. 2026. DOI: 10.2147/DDDT.S619901.
@article{c2026,
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},
note = {PMID: 42381975},
}
TY - JOUR AU - Zhang C AU - Fang D AU - Zhang L TI - Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification. T2 - Drug design, development and therapy PY - 2026 DO - 10.2147/DDDT.S619901 AN - PMID:42381975 ER -
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.