Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models  

作　　者：Kinya Matsuo Hideaki Nshihara 

机构地区：[1]Yamaguchi University Graduate School of Medicine,Yamaguchi,Japan [2]Department of Neurotherapeutics,Yamaguchi University,Ube,Japan

出　　处：《Neural Regeneration Research》2024年第9期1954-1960,共7页中国神经再生研究（英文版）

基　　金：supported by the Uehara Memorial Foundation,JSPS under the Joint Research Program implemented in association with SNSF(JRPs),Grant No.JPJSJRP20221507 and KAKENHI Grant No.22K15711,JST FOREST Program(Grant No.JPMJFR2269,Japan);2022 iPS Academia Japan Grant,Life Science Foundation of Japan,Kato Memorial Bioscience Foundation,THE YUKIHIKO MIYATA MEMORIAL TRUST FOR ALS RESEARCH,the ICHIRO KANEHARA FOUNDATION,Takeda Science Foundation,and the YAMAGUCHI UNIVERSITY FUNDATION(all to HN).

摘　　要：The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.

关 键 词：Alzheimer’s disease blood-brain barrier human induced pluripotent stem cells 

分 类 号：R749.16[医药卫生—神经病学与精神病学]