This study investigates TDP-43 dysregulation in VaD.<h4>Methods</h4>TDP-43 and phosphorylated TDP-43 (pTDP-43) expression and localization were assessed in a VaD animal model, neuronal cells exposed to oxygen-glucose deprivation (OGD), and post mortem human brain tissues.<h4>Results</h4>Bilateral Common Carotid Artery Stenosis (BCAS)-induced CCH led to increased pTDP-43 and aberrant redistribution of both TDP-43 and pTDP-43. Here, TARDBP is linked to columnar cell hyperplasia of the breast.