Age-dependent peripheral dissemination of α-synuclein seeds: mechanistic basis for blood-based early detection of Parkinson's disease - PubMed
3 days ago
- #Parkinson's Disease
- #Early Detection
- #α-Synuclein
- The study explores how misfolded α-synuclein (α-Syn) seeds spread from the brain to peripheral tissues in Parkinson's disease (PD) models, worsening with age and microglia involvement.
- Using α-Syn preformed fibril (PFF) mouse models, researchers found peripheral α-Syn dissemination occurs before motor symptoms, exacerbated in middle-aged mice, linked to neuroinflammation.
- Microglia depletion reduced central α-Syn accumulation and peripheral spread, highlighting activated microglia's role in disease progression and peripheral dissemination.
- A proof-of-concept human study applied serum α-Syn seed amplification assay (SAA) to isolated REM sleep behavior disorder (iRBD) patients, showing 64% sensitivity and 100% specificity when combined with BBB marker S100B.
- The findings suggest a mechanistic link between microglia-driven neuroinflammation, blood-brain barrier disruption, and peripheral α-Syn spread, supporting serum-based SAA as a potential early PD detection strategy.