Astrocytic-derived vascular remodeling factors are independently associated with blood brain barrier permeability in Alzheimer's disease.
Neurobiol Aging
; 141: 66-73, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38823205
ABSTRACT
Astrocytes in Alzheimer's disease (AD) exert a pivotal role in the maintenance of blood-brain barrier (BBB) integrity essentially through structural support and release of soluble factors. This study provides new insights into the vascular remodeling processes occurring in AD, and reveals, in vivo, a pathological profile of astrocytic secretion involving Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinases (MMP)-9, MMP-2 and Endothelin-1 (ET-1). Cerebrospinal fluid (CSF) levels of VEGF, MMP-2/-9 were lower in patients belonging to the AD continuum, compared to aged-matched controls. CSF levels of VEGF and ET-1 positively correlated with MMP-9 but negatively with MMP-2, suggesting a complex vascular remodeling process occurring in AD. Only MMP-2 levels were significantly associated with CSF AD biomarkers. Conversely, higher MMP-2 (ß = 0.411, p < 0.001), ET-1 levels (ß = 0.344, p < 0.001) and VEGF (ß = 0.221, p = 0.022), were associated with higher BBB permeability. Astrocytic-derived vascular remodeling factors are altered in AD, disclosing the failure of important protective mechanisms which proceed independently alongside AD pathology.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
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Astrocitos
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Endotelina-1
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Metaloproteinasa 2 de la Matriz
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Metaloproteinasa 9 de la Matriz
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Factor A de Crecimiento Endotelial Vascular
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Enfermedad de Alzheimer
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Remodelación Vascular
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neurobiol Aging
Año:
2024
Tipo del documento:
Article