Platelet Behavior Contributes to Neuropathologies: A Focus on Alzheimer's and Parkinson's Disease

Abstract

The functions of platelets are broad. Platelets function in hemostasis and thrombosis, inflammation and immune responses, vascular regulation, and host defense against invading pathogens, among others. These actions are achieved through the release of a wide set of coagulative, vascular, inflammatory, and other factors as well as diverse cell surface receptors involved in the same activities. As active participants in these physiological processes, platelets become involved in signaling pathways and pathological reactions that contribute to diseases that are defined by inflammation (including by pathogen-derived stimuli), vascular dysfunction, and coagulation. These diseases include Alzheimer's and Parkinson's disease, the two most common neurodegenerative diseases. Despite their unique pathological and clinical features, significant shared pathological processes exist between these two conditions, particularly relating to a central inflammatory mechanism involving both neuroinflammation and inflammation in the systemic environment, but also neurovascular dysfunction and coagulopathy, processes which also share initiation factors and receptors. This triad of dysfunction—(neuro)inflammation, neurovascular dysfunction, and hypercoagulation—illustrates the important roles platelets play in neuropathology. Although some mechanisms are understudied in Alzheimer's and Parkinson's disease, a strong case can be made for the relevance of platelets in neurodegeneration-related processes.

Association between 23 drugs and Parkinson's disease: A two‐sample Mendelian randomization study

“…Inhibition of platelet aggregation and thrombin is an important means of anti‐thrombosis. Inflammation promotes platelet aggregation in cerebral microvasculature, while soluble factors released by activated platelets in turn promote the development of inflammation (Page & Pretorius, 2022 ). Some antiplatelet drugs show promising results in the treatment of PD.…”

Platelet Dynamics in Neurodegenerative Disorders: Investigating the Role of Platelets in Neurological Pathology

“…While the intact mitochondrial membrane potential in PLTs from PD patients indicates compensatory mechanisms, it also suggests potential subtypes of PD. This emphasises the imperative need to explore various cell types, including PLTs, for a comprehensive understanding of PD pathophysiology [106,107].…”

The multifaceted role of platelets in mediating brain function

“…Neuroinflammation, which contributes to the pathophysiology of various neurological diseases, comprises a cascade of accumulating damage encompassing cellular and molecular components, including the generation of reactive oxygen species, the release of cytokines and chemokines, microglial and astrocytic activation, neuronal protein unfolding and aggregation, and neuronal cell death. 56,57 It is now becoming clear that systemic inflammation, neurovascular dysfunction, and coagulopathy coexist in neurological pathologies, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), 58,59 highlighting a likely role of the blood compartment in the detrimental inflammatory aspect of neurological diseases. The concept that the blood system is involved in the pathophysiology of brain neuroinflammation is supported by the high level of vascularization of the CNS parenchyma, which facilitates crosstalk between the blood and the brain, and the loss of integrity of the blood–brain barrier (BBB) that occurs in various chronic neurodegenerative disorders and as a consequence of brain trauma.…”