Blood-brain barrier breakdown in the aging human hippocampus

Axel Montagne, Samuel R Barnes, Melanie D Sweeney, Matthew R Halliday, Abhay P Sagare, Zhen Zhao, Arthur W Toga, Russell E Jacobs, Collin Y Liu, Lilyana Amezcua, Michael G Harrington, Helena C Chui, Meng Law, Berislav V Zlokovic

Research output: Contribution to journalArticlepeer-review

Abstract

UNLABELLED: The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens, and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates 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 temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment.

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Original languageEnglish
Pages (from-to)296-302
Number of pages7
JournalNeuron
Volume85
Issue number2
DOIs
Publication statusPublished - 21 Jan 2015

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging/metabolism
  • Albumins/cerebrospinal fluid
  • Blood-Brain Barrier/metabolism
  • Brain/metabolism
  • CA1 Region, Hippocampal/metabolism
  • CA3 Region, Hippocampal/metabolism
  • Case-Control Studies
  • Caudate Nucleus/metabolism
  • Cerebral Cortex/metabolism
  • Cognitive Dysfunction/metabolism
  • Dentate Gyrus/metabolism
  • Female
  • Hippocampus/metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neostriatum/metabolism
  • Pericytes/metabolism
  • Permeability
  • Serum Albumin
  • Thalamus/metabolism
  • Young Adult

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