Cerebral amyloid angiopathy occurs after stroke, but the mechanism underlying the initial amyloid-β deposition is not fully understood. This study investigates whether overexpression of fibronectin and its receptor, integrin-α5, induces the perivascular deposition of cerebrospinal fluid-derived amyloid-β 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-β deposition was enhanced in aged animals with stroke, which colocalized with integrin-α5 in the basement membrane. Furthermore, we found that stroke dramatically increased the cortical levels of fibronectin and integrin-α5, with further increases in integrin-α5 in aged animals with stroke, fibronectin bound amyloid-β in vitro, and fibronectin administration increased amyloid-β deposition in vivo. Finally, aging and stroke impaired performance on the Barnes maze. These results indicate that fibronectin induces the perivascular deposition of amyloid-β and that increased integrin-α5 further "primes" the aged brain for amyloid-β binding. This provides a novel molecular and physiological mechanism for perivascular amyloid-β deposition after stroke, particularly in aged individuals.
Keywords: Aging; Amyloid-β; Cerebral amyloid angiopathy; Extracellular; Fibronectin; Matrix; Stroke.
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