CSF TDP-43: A Novel Biomarker for Limbic-Predominant Age-Related TDP-43 Encephalopathy

Mislocalization and aggregation of transactive response DNA-binding protein 43 kDa (TDP-43) represent a neuropathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) and are increasingly recognized in Alzheimers disease (AD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). However, the in vivo value of CSF TDP-43 as a biomarker and its relation to established markers remains unclear. We quantified CSF concentrations of TDP-43 using ELISA in 25 controls, 32 ALS, 9 probable LATE, and 24 AD patients. CSF TDP-43 levels differed significantly between groups, with the highest concentrations in LATE, exceeding both ALS and AD. ALS and