Clinical study performed on patients with AD and mild cognitive impairment (MCI) observed enhanced BBB permeability by HMGB1 and suggest HMGB1 as a clinical biomarker as well as validates HMGB1 as a non-invasive biomarker of BBB dysfunction and neuroinflammation which can assess the progression of neurodegeneration in AD and MCI patients (Festoff et al., 2016). This evidence concerns the gene HMGB1 and Cognitive impairment.