TDP43

TDP43

The TAR DNA binding protein of 43 kDa (TDP43 or TARDBP) is a highly conserved and ubiquitously expressed nuclear protein with roles in transcription and splicing regulation. It is also the major component of ubiquitin-positive cytoplasmic inclusions found in the brains of patients with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In addition, TDP43-containing aggregates are found in a significant number of patients with Alzheimer’s Disease (AD) and other neuromuscular disorders. The majority of TDP43 protein found in cytoplasmic inclusions is truncated, and it has been shown that the C-terminal domain is intrinsically prone to aggregation. Mutations in the C-terminal region of the TDP43 gene have been associated with both ALS and FTLD, and are thought to facilitate ubiquitination and phosphorylation of the TDP43 protein, leading to the formation of pathological inclusions and eventual neurodegeneration. Analysis of TDP43 levels in plasma may allow the indexing of TDP43 pathology within the brain to aid in the diagnosis of different forms of dementia and distinguish between TDP43 proteinopathy and tauopathy. The Simoa TDP43 assay has been developed with a full-length protein calibrator and antibodies against AA 203 – 209 and the C-terminal region; it is expected to detect both full-length and pathological, truncated forms of the protein.