An important pathophysiological mechanism of cerebral small vessel disease is endothelium dysfunction and reduces the appearance of tight junctions (TJs) and adherens junctions (AJs), efflux transporter proteins important for cerebrovascular protection, leading to blood–brain barrier leakage [33]; therefore, we investigated a potential approach to identify the disease through circulating biological factors, such as SDF-1, a ligand of CXCR4. Here, CXCR4 is linked to cerebral small vessel disease.