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NYUAD researchers shed new light on mysteries behind the light emission of fireflies 新闻
来源平台:EurekAlert. 发布日期:2020
作者:  admin
收藏  |  浏览/下载:12/0  |  提交时间:2020/12/22
Tunable THz radiation from 3D topological insulator 新闻
来源平台:EurekAlert. 发布日期:2020
作者:  admin
收藏  |  浏览/下载:2/0  |  提交时间:2020/11/05
Plant-based diets shown to lower blood pressure even with limited meat and dairy 新闻
来源平台:EurekAlert. 发布日期:2020
作者:  admin
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Covid-19 Could Put China’s Clean Energy Agenda on Hold 科技报告
来源:Center for Strategic & International Studies. 出版年: 2020
作者:  Jane Nakano;  Lachlan Carey
收藏  |  浏览/下载:5/0  |  提交时间:2020/05/13
APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline 期刊论文
NATURE, 2020, 581 (7806) : 70-+
作者:  Doherty, Tiarnan A. S.;  Winchester, Andrew J.;  Macpherson, Stuart;  Johnstone, Duncan N.;  Pareek, Vivek;  Tennyson, Elizabeth M.;  Kosar, Sofiia;  Kosasih, Felix U.;  Anaya, Miguel;  Abdi-Jalebi, Mojtaba;  Andaji-Garmaroudi, Zahra;  Wong, E. Laine;  Madeo, Julien;  Chiang, Yu-Hsien;  Park, Ji-Sang;  Jung, Young-Kwang;  Petoukhoff, Christopher E.;  Divitini, Giorgio;  Man, Michael K. L.;  Ducati, Caterina;  Walsh, Aron;  Midgley, Paul A.;  Dani, Keshav M.;  Stranks, Samuel D.
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Breakdown of the blood-brain barrier in individuals carrying the epsilon 4 allele of the APOE gene, but not the epsilon 3 allele, increases with and predicts cognitive impairment and is independent of amyloid beta or tau pathology.


Vascular contributions to dementia and Alzheimer'  s disease are increasingly recognized(1-6). Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction(7), including the early clinical stages of Alzheimer'  s disease(5,8-10). The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer'  s disease(11-14), leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes(15-19), which maintain BBB integrity(20-22). It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles) are distinguished from those without APOE4 (epsilon 3/epsilon 3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-beta or tau pathology measured in cerebrospinal fluid or by positron emission tomography(23). High baseline levels of the BBB pericyte injury biomarker soluble PDGFR beta(7,8) in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-beta and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway(19) in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer'  s disease pathology, and might be a therapeutic target in APOE4 carriers.