At the same time, the cytoplasmic ZO-1 and ZO-2 where evenly distributed along the plasma membrane at the points of the cell-cell contacts.94 Apolipoprotein E4 (apoE4), a major risk factor for AD, has been shown to be involved in tight junction alteration as well.95 It has been shown that mice deficient in apoE have expressed BBB leakage. Here, APOE is linked to Alzheimer disease.