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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.


  
Improved estimates on global carbon stock and carbon pools in tidal wetlands 期刊论文
NATURE COMMUNICATIONS, 2020, 11 (1)
作者:  Ouyang, Xiaoguang;  Lee, Shing Yip
收藏  |  浏览/下载:4/0  |  提交时间:2020/05/13
Benefits and trade-offs of replacing synthetic fertilizers by animal manures in crop production in China: A meta-analysis 期刊论文
GLOBAL CHANGE BIOLOGY, 2019
作者:  Zhang, Xiaoying;  Fang, Qunchao;  Zhang, Tao;  Ma, Wenqi;  Velthof, Gerard L.;  Hou, Yong;  Oenema, Oene;  Zhang, Fusuo
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
ammonia emissions  crop yield  fertilizers  greenhouse gases  livestock manure  meta-analysis  soil type  trade-offs  
Newer and select maize, wheat, and rice varieties can help mitigate N footprint while producing more grain 期刊论文
GLOBAL CHANGE BIOLOGY, 2019
作者:  Ying, Hao;  Yin, Yulong;  Zheng, Huifang;  Wang, Yingcheng;  Zhang, Qingsong;  Xue, Yanfang;  Stefanovski, Darko;  Cui, Zhenling;  Dou, Zhengxia
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
agronomic and morphological traits  grain yield  newer varieties  reactive N losses  sustainability  
Methane emissions from contrasting urban freshwaters: Rates, drivers, and a whole-city footprint 期刊论文
GLOBAL CHANGE BIOLOGY, 2019
作者:  Ortega, Sonia Herrero;  Gonzalez-Quijano, Clara Romero;  Casper, Peter;  Singer, Gabriel A.;  Gessner, Mark O.
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
CH4 flux  greenhouse gas  land use  urban ecology  urban ponds  urbanization impact  
Long-term nitrogen addition modifies microbial composition and functions for slow carbon cycling and increased sequestration in tropical forest soil 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (10) : 3267-3281
作者:  Tian, Jing;  Dungait, Jennifer A. J.;  Lu, Xiankai;  Yang, Yunfeng;  Hartley, Iain P.;  Zhang, Wei;  Mo, Jiangming;  Yu, Guirui;  Zhou, Jizhong;  Kuzyakov, Yakov
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
biogeochemical cycling  C and N turnover  global climate change  microbial functional community  N deposition  tropical forest  
Carbon budgets of wetland ecosystems in China 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (6) : 2061-2076
作者:  Xiao, Derong;  Deng, Lei;  Kim, Dong-Gill;  Huang, Chunbo;  Tian, Kun
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/26
carbon emission  carbon sequestration  carbon stock  carbon uptake  climate  wetland  
Volatile emissions from thawing permafrost soils are influenced by meltwater drainage conditions 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (5) : 1704-1716
作者:  Kramshoj, Magnus;  Albers, Christian N.;  Svendsen, Sarah H.;  Bjorkman, Mats P.;  Lindwall, Frida;  Bjork, Robert G.;  Rinnan, Riikka
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/26
Arctic  biogenic volatile organic compounds  climate change  gas fluxes  meltwater drainage  permafrost  soil ecology  tundra  
Nitrous oxide emissions from inland waters: Are IPCC estimates too high? 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (2) : 473-488
作者:  Maavara, Taylor;  Lauerwald, Ronny;  Laruelle, Goulven G.;  Akbarzadeh, Zahra;  Bouskill, Nicholas J.;  Van Cappellen, Philippe;  Regnier, Pierre
收藏  |  浏览/下载:10/0  |  提交时间:2019/04/09
Global soil nitrous oxide emissions since the preindustrial era estimated by an ensemble of terrestrial biosphere models: Magnitude, attribution, and uncertainty 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (2) : 640-659
作者:  Tian, Hanqin;  Yang, Jia;  Xu, Rongting;  Lu, Chaoqun;  Canadell, Josep G.;  Davidson, Eric A.;  Jackson, Robert B.;  Arneth, Almut;  Chang, Jinfeng;  Ciais, Philippe;  Gerber, Stefan;  Ito, Akihiko;  Joos, Fortunat;  Lienert, Sebastian;  Messina, Palmira;  Olin, Stefan;  Pan, Shufen;  Peng, Changhui;  Saikawa, Eri;  Thompson, Rona L.;  Vuichard, Nicolas;  Winiwarter, Wilfried;  Zaehle, Soenke;  Zhang, Bowen
收藏  |  浏览/下载:17/0  |  提交时间:2019/04/09
global nitrogen cycle  greenhouse gas emission  nitrous oxide  process-based modeling  soil N2O emission