A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease.
J, Y. (2026). A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Soci. https://doi.org/10.1007/s10072-026-09343-3
J Y. A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Soci. 2026; doi: 10.1007/s10072-026-09343-3
J Y. A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease.[J]. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Soci. 2026. DOI: 10.1007/s10072-026-09343-3.
@article{j2026,
author = {Yang J},
title = {A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Soci},
year = {2026},
doi = {10.1007/s10072-026-09343-3},
note = {PMID: 42635841},
}
TY - JOUR AU - Yang J TI - A cerebrospinal fluid blood-brain barrier dysfunction score is associated with progression from mild cognitive impairment to Alzheimer's disease. T2 - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Soci PY - 2026 DO - 10.1007/s10072-026-09343-3 AN - PMID:42635841 ER -
BACKGROUND: Blood-brain barrier permeability-related alterations are increasingly recognised as an early process in Alzheimer's disease, but their prognostic value and candidate molecular markers remain unclear. METHODS: Using longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we derived a cerebrospinal fluid BBB permeability-related score and evaluated its association with progression from mild cognitive impairment (MCI) to clinically diagnosed Alzheimer's disease dementia using Kaplan-Meier and multivariable Cox analyses. We additionally performed two-sample Mendelian randomisation screening across 832 CSF proteins in FinnGen, with replication in Bellenguez et al. 2022. RESULTS: Among 134 MCI participants, the higher BBB permeability-related score group showed significantly faster progression to clinically diagnosed AD dementia (HR 1.73, 95% CI 1.10-2.74; p = 0.018), remaining significant after adjustment for CSF amyloid-beta, total-tau, and phosphorylated tau. CD226 (IVW OR 3.12; FDR = 0.018) and GFRα-1 (IVW OR 0.52; FDR = 0.009) were identified; CD226 showed directional consistency across datasets whereas GFRα-1 did not. CONCLUSIONS: A BBB permeability-related score is associated with longitudinal progression from MCI to clinically diagnosed AD dementia. CD226 is a biologically supported candidate signal; GFRα-1 is hypothesis-generating pending replication.