Abstract
INTRODUCTION
Vascular dementia (VaD) is a major therapeutic challenge. Tar DNA-binding protein 43 (TDP-43), known for its role in neurodegeneration, may contribute to VaD pathogenesis under chronic cerebral hypoperfusion (CCH). This study investigates TDP-43 dysregulation in VaD.
METHODS
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.
RESULTS
Bilateral Common Carotid Artery Stenosis (BCAS)-induced CCH led to increased pTDP-43 and aberrant redistribution of both TDP-43 and pTDP-43. In vitro OGD triggered similar mislocalization. Post mortem VaD brains showed no TDP-43 abnormalities, while Alzheimer’s and mixed dementia cases exhibited marked pathology.
DISCUSSION
TDP-43 dysregulation appears early in VaD under hypoperfusive stress, distinguishing it from other dementia subtypes. These findings indicate that TDP‑43 may warrant further investigation as a potential early molecular feature of VaD.
Full Article:Â https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71196
