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NIH-funded study finds gene therapy may restore missing enzyme in rare disease 新闻
来源平台:EurekAlert. 发布日期:2021
作者:  admin
收藏  |  浏览/下载:9/0  |  提交时间:2021/07/26
Oncotarget: Anti-hormonal treatment eligibility in granulosa cell tumors of the ovary 新闻
来源平台:EurekAlert. 发布日期:2021
作者:  admin
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A novel marker of adult human neural stem cells discovered 新闻
来源平台:EurekAlert. 发布日期:2021
作者:  admin
收藏  |  浏览/下载:9/0  |  提交时间:2021/03/29
New test traces DNA origins to monitor transplant rejection and reveal hidden cancers 新闻
来源平台:EurekAlert. 发布日期:2021
作者:  admin
收藏  |  浏览/下载:6/0  |  提交时间:2021/03/29
Food for thought: New maps reveal how brains are kept nourished 新闻
来源平台:EurekAlert. 发布日期:2021
作者:  admin
收藏  |  浏览/下载:7/0  |  提交时间:2021/03/12
Biodistribution of AAV gene transfer vectors in nonhuman primate 新闻
来源平台:EurekAlert. 发布日期:2021
作者:  admin
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Genetic differences important in Alzheimer's diagnosis 新闻
来源平台:EurekAlert. 发布日期:2020
作者:  admin
收藏  |  浏览/下载:3/0  |  提交时间:2020/12/22
Computer model can process disparate sources of clinical data to predict brain age 新闻
来源平台:EurekAlert. 发布日期:2020
作者:  admin
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Early detection of Alzheimer's disease with dynamic MRI measurement of glucose in brain 新闻
来源平台:EurekAlert. 发布日期:2020
作者:  admin
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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:26/0  |  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.