Grozdanov V, Bousset L, Hoffmeister M, et al. - Given that α-synuclein pathology represents the hallmark of Parkinson disease, researchers determined if pathologic α-synuclein is a particular trigger for excessive inflammatory responses in Parkinson disease. In primary human monocytes and a microglial cell line, the immune response to pathologic forms of α-synuclein was determined by evaluating cytokine release upon exposure. Robust inflammatory activation of human monocytes and microglial BV2 cells was induced by pathologic α-synuclein (mutations, aggregation). Stronger activation of monocytes was provoked by blood extracellular vesicles from Parkinson disease patients vs healthy controls. When stimulated by pathologic α-synuclein, monocytes from Parkinson disease patients exhibited dysregulation as well as hyperactivity in response. Experts concluded that excessive inflammatory responses to α-synuclein in Parkinson disease can be caused by a combined action of α-synuclein pathology and dysregulation of monocytes.