The role of brain vasculature in neurodegenerative disorders

被引：727

作者：

Sweeney, Melanie D. ^{[1
,3
]}

Kisler, Kassandra ^{[1
,3
]}

Montagne, Axel ^{[1
,3
]}

Toga, Arthur W. ^{[2
]}

Zlokovic, Berislav V. ^{[1
]}

机构：

[1] Univ Southern Calif, Keck Sch Med, Dept Physiol & Neurosci, Los Angeles, CA 90007 USA

[2] Univ Southern Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA USA

[3] Univ Southern Calif, Keck Sch Med, Stevens Inst Neuroimaging & Informat, Lab Neuro Imaging, Los Angeles, CA USA

来源：

NATURE NEUROSCIENCE | 2018年 / 21卷 / 10期

基金：

美国国家卫生研究院;

关键词：

CEREBRAL-BLOOD-FLOW; MILD COGNITIVE IMPAIRMENT; DIMINISHED GLUCOSE-TRANSPORT; ALZHEIMERS-DISEASE; NEUROVASCULAR DYSFUNCTION; MULTIPLE-SCLEROSIS; FUNCTIONAL HYPEREMIA; APOLIPOPROTEIN-E; P-GLYCOPROTEIN; RISK-FACTORS;

D O I：

10.1038/s41593-018-0234-x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Adequate supply of blood and structural and functional integrity of blood vessels are key to normal brain functioning. On the other hand, cerebral blood flow shortfalls and blood-brain barrier dysfunction are early findings in neurodegenerative disorders in humans and animal models. Here we first examine molecular definition of cerebral blood vessels, as well as pathways regulating cerebral blood flow and blood-brain barrier integrity. Then we examine the role of cerebral blood flow and blood-brain barrier in the pathogenesis of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. We focus on Alzheimer's disease as a platform of our analysis because more is known about neurovascular dysfunction in this disease than in other neurodegenerative disorders. Finally, we propose a hypothetical model of Alzheimer's disease biomarkers to include brain vasculature as a factor contributing to the disease onset and progression, and we suggest a common pathway linking brain vascular contributions to neurodegeneration in multiple neurodegenerative disorders.

引用

收藏

页码：1318 / 1331

页数：14

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