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

doi:10.3389/fnagi.2023.1170663

Aβ1-42-containing platelet-derived extracellular vesicle is associated with cognitive decline in Parkinson's disease

Front Aging Neurosci. 2023 Apr 14:15:1170663. doi: 10.3389/fnagi.2023.1170663. eCollection 2023.

Authors

Ziyu Wang¹, Yuanchu Zheng¹, Huihui Cai¹, Chen Yang¹, Siming Li¹, Hong Lv², Tao Feng^{1

3}, Zhenwei Yu⁴

Affiliations

¹ Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Clinical Diagnosis Department of Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ China National Clinical Research Center for Neurological Diseases, Beijing, China.
⁴ Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

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.

Keywords: Aβ1-42; Parkinson’s disease; activated platelet; cognitive decline; extracellular vesicles.