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

doi:10.1016/j.neuron.2014.12.032

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 journal › Article › peer-review

Abstract / Description of output

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.

VIDEO ABSTRACT:

Original language	English
Pages (from-to)	296-302
Number of pages	7
Journal	Neuron
Volume	85
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2014.12.032
Publication status	Published - 21 Jan 2015

Keywords / Materials (for Non-textual outputs)

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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10.1016/j.neuron.2014.12.032

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title = "Blood-brain barrier breakdown in the aging human hippocampus",

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.VIDEO ABSTRACT: ",

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

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doi = "10.1016/j.neuron.2014.12.032",

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AU - Montagne, Axel

AU - Barnes, Samuel R

AU - Sweeney, Melanie D

AU - Halliday, Matthew R

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AU - Zhao, Zhen

AU - Toga, Arthur W

AU - Jacobs, Russell E

AU - Liu, Collin Y

AU - Amezcua, Lilyana

AU - Harrington, Michael G

AU - Chui, Helena C

AU - Law, Meng

AU - Zlokovic, Berislav V

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N2 - 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.VIDEO ABSTRACT:

AB - 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.VIDEO ABSTRACT:

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ER -

Blood-brain barrier breakdown in the aging human hippocampus

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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