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A secretory vesicle failure in Parkinson’s disease occurs in human platelets

P. Montenegro, M. Pueyo, JN. Lorenzo, R. González-Brito, A. Méndez, R. Borges (La Laguna, Spain)

Meeting: 2022 International Congress

Abstract Number: 1368

Keywords: Parkinson’s, Parkinsonism, Vesicle monamine transporter(VMAT2)

Category: Parkinson's Disease: Molecular Mechanisms of Disease

Objective: Since platelets use similar, if not the same, mechanisms to accumulate serotonin (5-HT) as dopaminergic neurons to store DA in their VS; we wonder if a functional failure in the handling of 5-HT would reflect what is happening in dopaminergic neurons and in others of aminergic lineage. This could be diagnostic and prognostic platform.

Background: The presence of high cytosolic concentrations of dopamine (DA) and its metabolites in neurons has been associated with increased vulnerability associated with Parkinson’s disease (PD). More than 99% of the amines are confined to secretory vesicles (VS), making these structures crucial for keeping cytosolic DA low. Platelets have been used as cell models of various neurological diseases.

Method: We have used freshly isolated blood platelets from 70 patients with PD, 113 control individuals and 21 patients with parkinsonism (iatrogenic origin, multi-systemic atrophy, dementia associated with Lewy bodies, progressive supranuclear palsy or parkinsonism of vascular origin). We have carried out a functional assay of 5-HT handling in human platelets in which its basal content and its capacity for accumulation, secretion and spontaneous loss have been quantified.

Results: We found a drastic decrease in 5-HT content and uptake, as well as a decrease in thrombin-induced release in platelets from PD patients, but not in most cases of parkinsonism. Platelets from PD patients had impaired ability to retain 5-HT in SV.

Conclusion: These findings indicate a functional impairment of the SVs for amine handling in patients with PD. We will discuss its use of this technique as i) a biomarker, ii) its potential capacity for preclinical detection of PD and iii) how these tests can serve as a platform to screen disease-modifying drugs.

To cite this abstract in AMA style:

P. Montenegro, M. Pueyo, JN. Lorenzo, R. González-Brito, A. Méndez, R. Borges. A secretory vesicle failure in Parkinson’s disease occurs in human platelets [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/a-secretory-vesicle-failure-in-parkinsons-disease-occurs-in-human-platelets/. Accessed June 14, 2025.
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