TDP-43 Aggregation as a Feature of Vascular Dementia
Researchers show chronic cerebral hypoperfusion (CCH), a core feature of vascular dementia, triggers cytoplasmic mislocalization and hyperphosphorylation of TDP-43 (pTDP-43) in mouse and in vitro models while total TDP-43 levels remain stable. The work links TDP-43 proteopathy to vascular injury and associated processes such as oxidative stress, mitochondrial dysfunction, neuroinflammation, blood–brain barrier breakdown, and white-matter lesions, drawing parallels with TDP-43 pathology in ALS, frontotemporal dementia, and Alzheimer’s disease.
Why it mattersPTDP-43 accumulation after chronic cerebral hypoperfusion links vascular injury to proteopathy; add TDP-43 biomarkers to VaD trials.