APP and Alzheimer disease: AD patients often exhibit lower ejection fractions, lower cerebral blood flow velocities, and greater vascular resistance.208,209 CBH during ageing has been widely reported to contribute to AD pathogenesis.210 CBH directly enhances the synthesis and amyloidogenic processing of APP by increasing the activities of β-secretase and γ-secretase to produce Aβ.211 Additionally, CBH disrupts the integrity of BBB, impairing the clearance of Aβ from the brain via transcytosis.