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DOI | 10.1126/science.aav9518 |
Amyloid beta oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes | |
Nortley, Ross1; Korte, Nils1; Izquierdo, Pablo1; Hirunpattarasilp, Chanawee1; Mishra, Anusha2; Jaunmuktane, Zane3,4; Kyrargyri, Vasiliki1,9; Pfeiffer, Thomas1; Khennouf, Lila1; Madry, Christian1,10; Gong, Hui1; Richard-Loendt, Angela3; Huang, Wenhui5; Saito, Takashi6; Saido, Takaomi C.6; Brandner, Sebastian3,7; Sethi, Huma8; Attwell, David1 | |
2019-07-19 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6450页码:250-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England; USA; Germany; Japan; Greece |
英文摘要 | Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid beta (A beta) constricts brain capillaries at pericyte locations. This was caused by A beta generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by A beta could potentially reduce energy lack and neurodegeneration in AD. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000476479200045 |
WOS关键词 | A-BETA ; BLOOD-FLOW ; BRAIN ; PRECURSOR ; ENDOTHELIN-1 ; MICROVESSELS ; DYSFUNCTION ; PERFUSION ; DIAMETER ; DAMAGE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201891 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England; 2.Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA; 3.Natl Hosp Neurol & Neurosurg, Div Neuropathol, Queen Sq, London WC1N 3BG, England; 4.UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, Queen Sq, London WC1N 3BG, England; 5.Univ Saarland, CIPMM, Mol Physiol, D-66421 Homburg, Germany; 6.RIKEN, Ctr Brain Sci, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan; 7.UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England; 8.UCL Queen Sq Inst Neurol, Div Neurosurg, Queen Sq, London WC1N 3BG, England; 9.Hellenic Pasteur Inst, Dept Immunol, Mol Genet Lab, Athens 11521, Greece; 10.Charite, Inst Neurophysiol, D-10117 Berlin, Germany |
推荐引用方式 GB/T 7714 | Nortley, Ross,Korte, Nils,Izquierdo, Pablo,et al. Amyloid beta oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes[J]. SCIENCE,2019,365(6450):250-+. |
APA | Nortley, Ross.,Korte, Nils.,Izquierdo, Pablo.,Hirunpattarasilp, Chanawee.,Mishra, Anusha.,...&Attwell, David.(2019).Amyloid beta oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes.SCIENCE,365(6450),250-+. |
MLA | Nortley, Ross,et al."Amyloid beta oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes".SCIENCE 365.6450(2019):250-+. |
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