High-level cystatin F dimers in plasma rapidly aggravate cognitive impairment in 5XFAD transgenic mice, suggesting that circulatory cystatin F inhibits peripheral Aβ clearance and leads to deteriorated Aβ deposition in the brain, providing us with a potential therapeutic target for the elimination of Aβ in the periphery. The gene discussed is CST7; the disease is Cognitive impairment.