MAPT and Alzheimer disease: In a mouse model of AD, an increase in BBB permeability was recorded prior to senile plaque formation, and subsequent Aβ aggregation was associated with further degradation of BBB integrity.86 In humans, capillary damage and pericyte injury in hippocampal regions have been identified as the earliest signs of cognitive dysfunction among AD patients.87 Notably, in this study, early hippocampal BBB breakdown was independent of Aβ and p-tau burden.