Platelets in Neurodegenerative Diseases

Platelets play a significant role in neurodegenerative diseases (NDDs), and beyond their classical functions in hemostasis and thrombosis, they actively participate in chronic inflammation and neuroinflammation. Despite their different embryological origin, localization, and specific functions, parallels between platelets and neurons have been highlighted and make platelets valuable models for studying NDDs. Platelets contain proteins that are highly expressed in neurons, such as neurotrophic factors, amyloid precursor protein, amyloid peptides, α-synuclein, Tau, serotonin and biological amines, and prion protein that are central to NDD pathology. The physiological function of these proteins in platelets are not always clear, but platelet abnormalities has been described in patients affected of neurodegeneration. In this chapter, we describe the involvement of circulating platelets in the principal NDDs. Platelets are primary sources of circulating amyloid peptides and contribute to amyloid deposition in the brain and blood vessels in Alzheimer’s disease. Enhanced APP metabolism and altered secretase activity have been reported in Alzheimer’s disease platelets that correlate with disease progression. Also, Alzheimer’s disease platelets are preactivated and contribute to an increased risk of cardiovascular diseases. In Parkinson’s disease, platelets exhibit impaired aggregation, mitochondrial dysfunction, and altered α-synuclein dynamics, revealing their diagnostic potential. Emerging evidence also links platelet hyperreactivity to multiple sclerosis, with increased platelet aggregation and interaction with immune cells exacerbating neuroinflammatory processes. Studies on amyotrophic lateral sclerosis and Huntington’s disease have revealed mitochondrial perturbations and neurotransmitter imbalances in platelets, albeit with less conclusive findings. The involvement of platelets in prion diseases is less clear, but the presence of prion protein in platelets has been described. The dual role of platelets as biomarkers and contributors to NDD progression highlights their clinical importance. While they reflect neuronal dysfunction and offer accessible diagnostic tools, their involvement in thrombosis and inflammation presents therapeutic challenges. Understanding the mechanisms underlying platelet-related abnormalities in NDDs remains critical for advancing diagnostic and therapeutic strategies.