Neurovascular large artery dilatation increases the risk for Alzheimer's disease pathology

mice, a model of amyloid pathology, by injecting elastase into the cisterna magna. Mice were euthanized at 9 months and brains were analyzed using biochemical and immunohistochemical approaches. Elastase-treated mice showed a significant increase in amyloid plaque burden in the hippocampus and cortex compared with vehicle-treated controls. Neuronal loss was observed in the CA1 region of the hippocampus, with a similar trend in CA3. Markers of impaired autophagic-lysosomal clearance were elevated in both hippocampal and cortical regions, while neuroinflammation and astrogliosis were unchanged. In contrast, matrix metalloproteinase-9 (MMP-9) levels were significantly increased. Overall, this study establishes a novel mixed vascular-neurodegenerative pathology model by inducing large artery dilatation in an amyloid mouse model. Our findings demonstrate that vascular dilatation accelerates Alzheimer's disease-related pathology and provide a platform to investigate underlying mechanisms and potential therapeutic targets for mixed dementia.