Alternative platelet activation pathways and their role in neurodegenerative diseases

The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathways in the development of these diseases. Platelets participate in synaptic plasticity, learning, memory, and platelets activated by exercise promote neuronal differentiation in several brain regions. Platelets also contribute to the immune response by modulating their surface protein profile and releasing pro- and anti-inflammatory mediators. In Alzheimer's disease, increased levels of platelet amyloid precursor protein raise the production of amyloid-beta peptides promoting platelet activation, triggering at the same time amyloid-beta fibrillation. In Parkinson's disease, increased platelet α-synuclein is associated with elevated ROS production and mitochondrial dysfunction. In this review, we revise different platelet activation pathways, those classically involved in hemostasis and wound healing, and alternative activation pathways recently described in the context of neurodegenerative diseases, especially in Alzheimer's disease. •Platelet functions go beyond hemostasis and wound healing.•Alternative platelet activation pathways are associated with brain function.•In Alzheimer's disease, increased amyloid-beta peptides promote platelet activation.•In Parkinson's disease, increased platelet α-syn leads to mitochondrial dysfunction.