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

ABSTRACT: Cerebral amyloid angiopathy occurs after stroke, but the mechanism underlying the initial amyloid-? deposition is not fully understood. This study investigates whether overexpression of fibronectin and its receptor, integrin-?5, induces the perivascular deposition of cerebrospinal fluid-derived amyloid-? 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-? deposition was enhanced in aged animals with stroke, which colocalized with integrin-?5 in the basement membrane. Furthermore, we found that stroke dramatically increased the cortical levels of fibronectin and integrin-?5, with further increases in integrin-?5 in aged animals with stroke, fibronectin bound amyloid-? in vitro, and fibronectin administration increased amyloid-? deposition in vivo. Finally, aging and stroke impaired performance on the Barnes maze. These results indicate that fibronectin induces the perivascular deposition of amyloid-? and that increased integrin-?5 further "primes" the aged brain for amyloid-? binding. This provides a novel molecular and physiological mechanism for perivascular amyloid-? deposition after stroke, particularly in aged individuals.

SUBMITTER: Howe MD 

PROVIDER: S-EPMC6219378 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature