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Introduction: Ischemic stroke is a major risk factor for cerebral amyloid angiopathy (CAA), which may be driven by alterations in the paravascular transport of cerebrospinal fluid (CSF) amyloid-β1-40(Aβ40) through the basement membrane (BM). Post-stroke BM thickening may favor CSF Aβ40 deposition within brain microvessels. This study identifies BM fibronectin (FN) and its receptor, α5β1 integrin, as novel drivers of paravascular Aβ40 deposition after stroke in aged animals.Hypothesis: We hypothesize that stroke-induced FN expression induces paravascular deposition of CSF Aβ40 within the brain. This may worsen with aging due to increased FN binding to α5β1 integrin.Methods: Young (3 months-old) and aged (18 months-old) male mice were subjected to experimental stroke, and fluorescent tracers were intracisternally microinjected 30 days later to measure brain uptake of CSF Aβ40. BM thickening (lectin staining), as well as endogenous levels of FN and α5β1 integrin, were measured by immunohistochemistry and Western blot. To assess FN-Aβ40 binding, naïve young and aged mice were intracisternally injected with FN or vehicle, and Aβ40 uptake from CSF measured. Statistical significance was confirmed by two-way ANOVA with Dunnet’s post-hoc test.Results: Stroke enhanced paravascular Aβ40 deposition compared to size-matched dextran in young animals (p<.05), which worsened with aging (p<.001). Interestingly, BM thickening positively correlated with paravascular Aβ40deposition after stroke in both age groups (R=.98, p<.001). Furthermore, FN levels increased in both young (p<.05) and aged (p<.05) cortex after stroke, with additional increases seen in α5β1 integrin expression in aged cortex at baseline (p<.05) and with stroke (p<.01). Finally, FN exhibited affinity for Aβ40in vitro (IC50= 216nM), and FN infusion increased paravascular Aβ40 deposition in vivo (p<.05), which worsened with aging (p<.05).Conclusion: These results indicate that FN induces paravascular Aβ40 deposition after stroke. Furthermore, increased α5β1 integrin may ‘prime’ the aged vasculature for FN-Aβ binding, worsening Aβ40 deposition after stroke in aged animals. Targeting FN-Aβ adhesion may provide a novel therapeutic avenue to reduce CAA in stroke survivors.