Fibronectin induces the perivascular deposition of cerebrospinal fluid-derived amyloid-β in aging and after stroke

NEUROBIOLOGY OF AGING

卷:72

Article

Howe, Matthew D.¹  Atadja, Louise A.¹  Furr, J. Weldon¹  Maniskas, Michael E.¹  Zhu, Liang¹  McCullough, Louise D.¹  Urayama, Akihiko¹ 

[1] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Neurol, 6431 Fannin St, Houston, TX 77030 USA

关键词: Cerebral amyloid angiopathy;    Stroke;    Aging;    Extracellular;    Matrix;    Amyloid-beta;    Fibronectin;   

DOI  :  10.1016/j.neurobiolaging.2018.07.019

来源: Elsevier

【 摘 要 】

Cerebral amyloid angiopathy occurs after stroke, but the mechanism underlying the initial amyloid-beta deposition is not fully understood. This study investigates whether overexpression of fibronectin and its receptor, integrin-alpha 5, induces the perivascular deposition of cerebrospinal fluid-derived amyloid-beta after stroke in young and aged animals. We found that stroke impaired the bulk flow of cerebrospinal fluid into the brain parenchyma and further showed that perivascular amyloid-beta deposition was enhanced in aged animals with stroke, which colocalized with integrin-alpha 5 in the basement membrane. Furthermore, we found that stroke dramatically increased the cortical levels of fibronectin and integrin-alpha 5, with further increases in integrin-alpha 5 in aged animals with stroke, fibronectin bound amyloid-beta in vitro, and fibronectin administration increased amyloid-beta deposition in vivo. Finally, aging and stroke impaired performance on the Barnes maze. These results indicate that fibronectin induces the perivascular deposition of amyloid-beta and that increased integrin-alpha 5 further primes the aged brain for amyloid-beta binding. This provides a novel molecular and physiological mechanism for perivascular amyloid-beta deposition after stroke, particularly in aged individuals. (C) 2018 Elsevier Inc. All rights reserved.

【 授权许可】

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