Alteraciones de las caveolas en las demencias tipo Alzheimer y por cuerpos de lewy: mecanismos de disfunción vascular y neurodegeneración
Caveola alterations in Alzheimer’s and lewy body dementias: mechanisms of vascular dysfunction and neurodegeneration
Resumen
RESUMEN
Objetivo: Sintetizar la evidencia científica sobre el papel de las caveolas y la caveolina-1 (Cav-1) en la fisiopatología de la barrera hematoencefálica (BHE) en la enfermedad de Alzheimer (EA) y la demencia por cuerpos de Lewy (DCL). Metodología: Se realizó una búsqueda sistemática en PubMed, Scopus y Web of Science (2019-2024) utilizando términos como "Caveolae", "Caveolin-1", "Blood-Brain Barrier", "Alzheimer Disease" y "Lewy Body Disease". Resultados: La literatura confirma la expresión pancelular de Cav-1 en el sistema nervioso central. En la EA, la desregulación de Cav-1 produce: aumento de transcitosis de fibrinógeno, activación de la vía Cav-1/MMP2/9 que degrada uniones estrechas, modulación de neuroinflamación y alteración del metabolismo lipídico en astrocitos APOE4. En la DCL, la internalización de α-sinucleína en neuronas dopaminérgicas depende de caveolas mediante el complejo FABP3/receptor D2L. Conclusiones: Cav-1 constituye un nodo molecular crítico en la disfunción de la BHE en demencias. La modulación específica de su dominio de andamiaje emerge como diana terapéutica prometedora.
ABSTRACT
Objective: To synthesize the scientific evidence on the role of caveolae and caveolin-1 (Cav-1) in the pathophysiology of the blood-brain barrier (BBB) in Alzheimer's disease (AD) and Lewy body dementia (LBD). Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science (2019-2024) using terms such as "Caveolae," "Caveolin-1," "Blood-Brain Barrier," "Alzheimer Disease," and "Lewy Body Disease." Results: The literature confirms the pan-cellular expression of Cav-1 in the central nervous system. In AD, Cav-1 dysregulation produces: increased fibrinogen transcytosis, activation of the Cav-1/MMP2/9 pathway degrading tight junctions, modulation of neuroinflammation, and altered lipid metabolism in APOE4 astrocytes. In LBD, α-synuclein internalization in dopaminergic neurons depends on caveolae through the FABP3/D2L receptor complex. Conclusions: Cav-1 constitutes a critical molecular node in BBB dysfunction in dementias. Specific modulation of its scaffolding domain emerges as a promising therapeutic target.
Recibido: 25-01-2026.
Aceptado: 04-03-2026.
Publicado: 29-05-2026
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Depósito Legal Electrónico: ME2016000090
ISSN Electrónico: 2610-797X
DOI: https://doi.org/10.53766/GICOS
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