Insights into the transcriptomic heterogeneity of brain endothelial cells in normal aging and Alzheimer's disease
Qian Yue1
Shang Li2
Chon Lok Lei3
Huaibin Wan4
Zaijun Zhang5
Maggie Pui Man Hoi6
1.The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People's Hospital),Heyuan,Guangdong Province,China;Department of Cardiology,The First Affiliated Hospital of Jinan University,Guangzhou,Guangdong Province,China;State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao Special Administrative Region,China;Department of Pharmaceutical Sciences,Faculty of Health Sciences,University of Macau,Macao Special Administrative Region,China2.Laboratory for Accelerated Vascular Research,Department of Surgery,University of California San Francisco,San Francisco,CA,USA3.Department of Biological Sciences,Faculty of Health Sciences,University of Macau,Macao Special Administrative Region,China4.The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People's Hospital),Heyuan,Guangdong Province,China5.State Key Laboratory of Bioactive Molecules and Druggability Assessment,and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases,and Institute of New Drug Research,Jinan University,Guangzhou,Guangdong Province,China;Guangdong-Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research,and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,Jinan University College of Pharmacy,Guangzhou,Guangdong Province,China;International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE),Jinan University College of Pharmacy,Guangzhou,Guangdong Province,China6.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao Special Administrative Region,China;Department of Pharmaceutical Sciences,Faculty of Health Sciences,University of Macau,Macao Special Administrative Region,China
摘要：Drug development for Alzheimer's disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer's disease in the Phase Ⅲ clinical trial(Clarity Alzheimer's disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer's disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer's disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer's disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer's disease progression.
机标关键词：alzheimerinsightsnormalcellsbrainagingdiseaseendothelial
论文发表日期：2026-02-28
在线出版日期：2025-12-09（本平台首次上网日期，不代表文献的发表时间）
页数：8( 569-576 )
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