Aβ1-42-containing platelet-derived extracellular vesicle is associated with cognitive decline in Parkinson’s disease
Ziyu Wang, Yuanchu Zheng, Huihui Cai, Chen Yang, Siming Li, Hong Lv, Tao Feng, Zhenwei Yu
Abstract
Background Cortical amyloid deposition is a common observation in Parkinson’s disease dementia (PDD) patients. Aβ1-42 is linked to a more rapid progression of dementia. Platelets, which degranulate upon activation, are a primary source of Aβ. It has been repeatedly reported that peripheral extracellular vesicles (EVs) can partially reach the central nervous system. Thus, we speculate that activated platelet-derived Aβ1-42-containing EVs (PEV-Aβ1-42) play a crucial role in the cognitive decline of PD patients. Methods The study included 189 participants: 66 with non-dementia PD, 73 with PDD, and 50 healthy controls. All participants underwent blood collection and clinical assessments. Twenty PD patients underwent re-examination and repeated blood collection 14 months later. A nano-scale flow cytometry assay was used to detect PEVs and PEV-Aβ1-42 using fluorescence-labeled CD62P and Aβ1-42 antibodies. Results Parkinson’s disease dementia patients had higher PEV-Aβ1-42 concentrations than healthy controls ( p = 0.028). The ratio of PEV-Aβ1-42 to PEV was significantly higher in PDD patients compared to those in non-dementia PD and healthy controls ( p PD-ND < 0.001, p HC = 0.041). The PEV-Aβ1-42/PEV ratio appears to influence the odds of developing dementia (OR = 1.76, p < 0.001). The change in the PEV-Aβ1-42/PEV ratio was also correlated with cognitive decline over 14 months ( r = −0.447, p < 0.05). Conclusion The plasma PEV-Aβ1-42/PEV ratio may serve as a diagnostic and prognostic biomarker for PDD patients.