Blood-brain barrier breakdown in the aging human hippocampus.

The blood-brain barrier (BBB) limits entry of blood-derivedproducts,pathogens,andcellsintothebrainthat is essential for normal neuronal functioning andinformationprocessing.Post-mortemtissueanalysisindicates BBB damage in Alzheimer’s disease (AD).The timing of BBB breakdown remains, however,elusive. Using an advanced dynamic contrast-enhanced MRI protocol with high spatial and tempo-ral resolutions to quantify regional BBB permeabilityinthelivinghumanbrain,weshowanage-dependentBBB breakdown in the hippocampus, a region crit-ical for learning and memory that is affected early inAD. The BBB breakdown in the hippocampus andits CA1 and dentate gyrus subdivisions worsenedwith mild cognitive impairment that correlated withinjury to BBB-associated pericytes, as shown bythe cerebrospinal fluid analysis. Our data suggestthat BBB breakdown is an early event in the aginghuman brain that begins in the hippocampus andmay contribute to cognitive impairment.