AUTHOR=Wang Ziyu , Zheng Yuanchu , Cai Huihui , Yang Chen , Li Siming , Lv Hong , Feng Tao , Yu Zhenwei 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1170663

DOI=10.3389/fnagi.2023.1170663

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>Parkinson’s disease dementia patients had higher PEV-Aβ1-42 concentrations than healthy controls (<italic>p</italic> = 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 (<italic>p</italic><sub>PD-ND</sub> &lt; 0.001, <italic>p</italic><sub>HC</sub> = 0.041). The PEV-Aβ1-42/PEV ratio appears to influence the odds of developing dementia (OR = 1.76, <italic>p</italic> &lt; 0.001). The change in the PEV-Aβ1-42/PEV ratio was also correlated with cognitive decline over 14 months (<italic>r</italic> = −0.447, <italic>p</italic> &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>The plasma PEV-Aβ1-42/PEV ratio may serve as a diagnostic and prognostic biomarker for PDD patients.</p></sec>