TDP43 protein in cerebral amyloid angiopathy in APOE heterozygotes

Transactive response DNA-binding protein 43 (TDP-43) is a protein that in humans is encoded by the TAR DBP gene. TDP-43 is expressed nuclear protein that binds both DNA and RNA, and is shuttling between nucleus and cytoplasm of neurons and neuroglial cells, regulating many aspects of RNA processing. In aging and some neurodegenerative diseases including limbic-predominant age-related TDP-43 encephalopathy (LATE) the TDP-43 protein is aggregated in neurons and the glial cells forming pathological inclusions. It has been reported that some genes, including gen APOE contributes to the formation of these pathological aggregates of TDP43 protein. Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid β-peptide. The normal function of β-amyloid is not exactly known. A strong relationship between the APOE ε-3/4 alleles and the presence of CAA were observed. The apoE is a polymorphic protein that plays a central role in metabolism of cholesterol and the triglycerides. We tested, if in cases of CAA disease with APOE ε-3/4 (it was the most common), pathological deposites of TDP43 proteins were observed in the human brains. In most of the CAA cases studied (18/20), the antiTDP-43 antibody recognized pathological inclusions in the nuclei and neuronal cytoplasm, neurites in vascular endothelial cells and astrocytes.