Infiltration of immune cells to the brain and its relation to the pathogenesis of Alzheimer's and Parkinson's diseases

The neurovascular unit, composed of vascular endothelium, vascular smooth muscle, extracellular matrix components, pericytes, astrocytes, microglia, and neurons, allows the highly regulated exchange of molecules and the limited trafficking of cells to the brain through coordinated signaling activity. The passage of peripheral immune cells to the brain parenchyma is observed when there is clear damage to the barriers of this neurovascular unit, as occurs in traumatic brain injury. The possibility of leukocyte infiltration to the brain in neurodegenerative conditions has been proposed. In this review, we focus on describing the evidence for peripheral immune cell infiltration to the brain in the two most frequent neurodegenerative diseases: Alzheimer's and Parkinson's diseases. In particular, we address the mechanisms that promote the passage of these cells into the brain under such pathological conditions. We also discuss the relevance of the resulting cellular interactions, which provide evidence that the presence of peripheral immune cells in the brain is a key point in these neurodegenerative diseases. The disruption of the neurovascular unit and the infiltration of the peripheral immune cells into the central nervous system are hallmarks of neurodegenerative diseases. However, so far, the participation of infiltrating cells in the progression of these diseases has not been completely defined. In this work, we gather the evidence that exists until now which proposes the key events involved in the pathogenesis of the two main neurodegenerative diseases: Alzheimer's and Parkinson's diseases. We detail the alterations in the components that typically keep the neurovascular unit semi-permeable to the cellular interactions that promote a self-perpetuating cycle of inflammation.image