The transactive response region DNA-binding protein 43 (TDP43) binds both DNA and RNA and is involved in transcription and splicing. Under pathophysiological conditions, TDP43 accumulates in the cytoplasm and is hyperphosphorylated and/ or ubiquitinated, and this is Characteristic of the cytoplasmic inclusions observed in ALS and in many cases of frontotemporal labor degeneration syndrome (FTLD). Furthermore, TDP43 pathology is also detected in 20-50 %of AD patients, and appears to be associated with greater brain atrophy, memory loss, and cognitive impairment.
Prominent physiological nuclear immunostaining of TDP43 and a neuronal cytoplasmic inclusion body in a neuron lacking the physiological nuclear staining (arrow) using 2G10 antibody in a case with FTLD-TDP (G.G. Kovacs, Toronto, Canada).
Fine neuropil threads in the hippocampus and neuronal cytoplasmic inclusions detected by 2G10 in an AD case with concomitant limbicTDP43 protein pathology (G.G. Kovacs, Toronto, Canada).