The glymphatic system and Parkinson's disease: a narrative review
NEUROLOGICAL SCIENCES, cilt.47, sa.8, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Derleme
- Cilt numarası: 47 Sayı: 8
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10072-026-09291-y
- Dergi Adı: NEUROLOGICAL SCIENCES
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, Index Islamicus, MEDLINE, Psycinfo, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest), Psychology & Behavioral Sciences Collection (EBSCO)
- İstanbul Üniversitesi Adresli: Evet
Özet
Background The glymphatic system, a glia-dependent perivascular fluid transport pathway, has provided new insights into brain homeostasis and neurodegeneration. Although Parkinson's disease (PD) is classically defined by dopaminergic neuronal loss and alpha-synuclein aggregation, impaired clearance of metabolic waste via glymphatic pathways may contribute to its pathophysiology. Advances in neuroimaging, particularly Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS), now enable in vivo assessment of glymphatic-related alterations.Methods This narrative review synthesizes current experimental, imaging, and clinical evidence on glymphatic dysfunction in PD. We focus on DTI-ALPS as a surrogate marker of glymphatic activity, examining its relationship with motor and non-motor features, and its potential as a biomarker. Methodological and conceptual limitations are also considered.Results Reduced DTI-ALPS indices are frequently reported in PD and correlate with greater motor severity and cognitive impairment, providing indirect, diffusion-based evidence that perivascular fluid transport is altered in this disease. These findings support a role for glymphatic dysfunction in disease burden and progression. Mechanistically, impaired perivascular clearance may promote the accumulation of misfolded alpha-synuclein and other neurotoxic metabolites. However, the specificity of DTI-ALPS as a direct measure of glymphatic function remains debated, and its relationship with vascular pathology and structural brain changes requires further clarification.Conclusions Glymphatic dysfunction represents a promising but evolving framework in PD. Understanding its interaction with alpha-synuclein pathology and vascular integrity may facilitate the development of imaging biomarkers and disease-modifying strategies. Longitudinal and standardized studies are needed to establish clinical relevance.