Interconnected roles of astrocytes and the blood-brain barrier in Parkinson's disease: pathological evidence, mechanistic insights, and knowledge gaps - PubMed

4 hours ago

Parkinson's disease (PD) involves α-synuclein aggregation and dopaminergic neurodegeneration, with growing evidence pointing to astrocytes and the blood-brain barrier (BBB) as key contributors.
Human studies show BBB disruption and astrocytic abnormalities in PD, including plasma protein extravasation, tight junction alterations, and microvascular degeneration in the substantia nigra and striatum.
Neuroimaging and biomarkers like elevated QAlb, plasma GFAP, and CSF S100B support vascular compromise and astrocytic reactivity in PD.
Animal and cell-based models reveal that BBB breakdown can precede or parallel dopaminergic loss, with disrupted astrocyte morphology and altered inflammatory signaling.
Astrocytic pathways can either worsen or mitigate BBB dysfunction, highlighting a bidirectional astrocyte-vascular axis in PD pathology.
Key knowledge gaps include limited longitudinal human data, unclear temporal ordering, and the need for integrative approaches to determine if astrocyte/BBB dysfunction drives PD progression or is a secondary response.
Therapeutic potential lies in targeting astrocyte and BBB dysfunction, but further research is needed to validate these approaches.

Hasty Briefsbeta