Blood-brain barrier breakdown in the aging human hippocampus.

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Abstract

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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Journal

Journal ID (iso-abbrev): Neuron

Title: Neuron

ISSN (Electronic): 1097-4199

ISSN (Print): 0896-6273

Publication date (Electronic): Jan 21 2015

Volume: 85

Issue: 2

Affiliations

[1 ] Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.

[2 ] Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, CA 91101, USA.

[3 ] Institute for Neuroimaging & Informatics, Department of Neurology, University of Southern California, Los Angeles, CA 90089, USA.

[4 ] Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Department of Radiology, Neuroradiology Division, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.

[5 ] Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.

[6 ] Huntington Medical Research Institute, Pasadena, CA 91101, USA.

[7 ] Department of Radiology, Neuroradiology Division, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.

[8 ] Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: zlokovic@usc.edu.

Article

Publisher Item ID: S0896-6273(14)01141-6 Mid ID: NIHMS651289

DOI: 10.1016/j.neuron.2014.12.032

PubMed ID: 25611508

SO-VID: bd7fab7c-c44d-4cc7-b608-7f599197b272

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