Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

被引：1466

作者：

Montagne, Axel ^{[1
,2
]}

Barnes, Samuel R. ^{[3
]}

Sweeney, Melanie D. ^{[1
,2
]}

Halliday, Matthew R. ^{[1
,2
]}

Sagare, Abhay P. ^{[1
,2
]}

Zhao, Zhen ^{[1
,2
]}

Toga, Arthur W. ^{[4
]}

Jacobs, Russell E. ^{[3
]}

Liu, Collin Y. ^{[5
,6
]}

Amezcua, Lilyana ^{[5
]}

Harrington, Michael G. ^{[7
]}

Chui, Helena C. ^{[5
]}

Law, Meng ^{[6
]}

Zlokovic, Berislav V. ^{[1
,2
]}

机构：

[1] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA

[2] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90089 USA

[3] CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91101 USA

[4] Univ So Calif, Dept Neurol, Inst Neuroimaging & Informat, Los Angeles, CA 90089 USA

[5] Univ So Calif, Keck Sch Med, Dept Neurobiol, Los Angeles, CA 90089 USA

[6] Univ So Calif, Keck Sch Med, Neuroradiol Div, Dept Radiol, Los Angeles, CA 90089 USA

[7] Huntington Med Res Inst, Pasadena, CA 91101 USA

来源：

NEURON | 2015年 / 85卷 / 02期

基金：

美国国家卫生研究院;

关键词：

ALZHEIMERS-DISEASE BRAIN; VASCULAR CELLS; PERICYTES; PERMEABILITY; DISRUPTION; INTEGRITY; NEURODEGENERATION; CYCLOPHILIN; DISORDERS; GENOTYPE;

D O I：

10.1016/j.neuron.2014.12.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 showan 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.

引用

页码：296 / 302

页数：7

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