Fibrillar tau alters cerebral endothelial cell metabolism, vascular inflammatory activation, and barrier function in vitro and in vivo DOI Creative Commons
Roberto Guzmán‐Hernández, Silvia Fossati

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(3)

Опубликована: Март 1, 2025

Abstract INTRODUCTION The presence of tau aggregates in and around the brain vasculature Alzheimer's disease (AD) tauopathies suggests its possible pathogenicity to cerebral endothelial cells (ECs). METHODS We used an vitro model blood–brain barrier (BBB) understand mechanisms fibrillar tau–mediated EC BBB pathology, confirming our findings 3‐month‐old P301S mice brains extracted microvessels. RESULTS Protofibrillar species induce permeability through increase glycolysis, which activates ECs toward a pro‐inflammatory phenotype, inducing loss junction protein expression localization. Warburg‐like metabolic shift glycolysis increased vascular pathological phenotypes are also present young mice. DISCUSSION In sum, work reveals that species, by enhancing glycolytic metabolism, promote inflammatory function, highlighting importance addressing targeting early tau‐mediated neurovascular damage AD tauopathies. Highlights improve understanding pathology Fibrillar mediates changes, inflammation, dysfunction. These events replicated at stages tauopathy mouse model. Inhibiting altered reduces activation.

Язык: Английский

Fibrillar tau alters cerebral endothelial cell metabolism, vascular inflammatory activation, and barrier function in vitro and in vivo DOI Creative Commons
Roberto Guzmán‐Hernández, Silvia Fossati

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(3)

Опубликована: Март 1, 2025

Abstract INTRODUCTION The presence of tau aggregates in and around the brain vasculature Alzheimer's disease (AD) tauopathies suggests its possible pathogenicity to cerebral endothelial cells (ECs). METHODS We used an vitro model blood–brain barrier (BBB) understand mechanisms fibrillar tau–mediated EC BBB pathology, confirming our findings 3‐month‐old P301S mice brains extracted microvessels. RESULTS Protofibrillar species induce permeability through increase glycolysis, which activates ECs toward a pro‐inflammatory phenotype, inducing loss junction protein expression localization. Warburg‐like metabolic shift glycolysis increased vascular pathological phenotypes are also present young mice. DISCUSSION In sum, work reveals that species, by enhancing glycolytic metabolism, promote inflammatory function, highlighting importance addressing targeting early tau‐mediated neurovascular damage AD tauopathies. Highlights improve understanding pathology Fibrillar mediates changes, inflammation, dysfunction. These events replicated at stages tauopathy mouse model. Inhibiting altered reduces activation.

Язык: Английский

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