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Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease
Yue, Qian1,2; Hoi, Maggie Pui Man1,2
2023-09-01
Source PublicationNeural Regeneration Research
ISSN1673-5374
Volume18Issue:9Pages:1890-1902
AbstractBlood-brain barrier disruption occurs in the early stages of Alzheimer's disease. Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer's disease progression. Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier. For example, astrocytic coverage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions. Astrocyte activation is often observed in Alzheimer's disease patients, with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta. Structural alterations in Alzheimer's disease astrocytes including swollen endfeet, somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arterioles levels. In addition, Alzheimer's disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration. In this review, we summarize the findings of existing literature on the relevance of astrocyte alteration in response to amyloid pathology in the context of blood-brain barrier dysfunction. First, we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance. Then, we review the clinical evidence of astrocyte pathology in Alzheimer's disease patients and the preclinical evidence in animal and cellular models. We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer's disease astrocyte. Finally, we evaluate the roles of soluble factors secreted by Alzheimer's disease astrocytes, providing potential molecular mechanisms underlying blood-brain barrier modulation. We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer's disease.
KeywordAlzheimer's disease amyloid-beta astrocyte (astroglial)-endothelial interaction astrocyte pathology blood-brain barrier blood-brain barrier disruption brain endothelial cell neuroinflammation reactive astrocyte
DOI10.4103/1673-5374.367832
URLView the original
Language英語English
Scopus ID2-s2.0-85150244009
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region, Macao
2.Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region, Macao
First Author AffilicationInstitute of Chinese Medical Sciences;  Faculty of Health Sciences
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GB/T 7714
Yue, Qian,Hoi, Maggie Pui Man. Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease[J]. Neural Regeneration Research, 2023, 18(9), 1890-1902.
APA Yue, Qian., & Hoi, Maggie Pui Man (2023). Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease. Neural Regeneration Research, 18(9), 1890-1902.
MLA Yue, Qian,et al."Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease".Neural Regeneration Research 18.9(2023):1890-1902.
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